AustralieFrV1, Ncbi, Checkpoint, bibRecord, 003897

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture

Identifieur interne : 003897 ( Ncbi/Checkpoint ); précédent : 003896; suivant : 003898

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture

Auteurs : Fanny Grillet [France] ; Elsa Bayet [France] ; Olivia Villeronce [France] ; Luke Zappia [Australie] ; Ebba Louise Lagerqvist [France] ; Sebastian Lunke [Australie] ; Emmanuelle Charafe-Jauffret [France] ; Kym Pham [Australie] ; Christina Molck [Australie] ; Nathalie Rolland [France] ; Jean François Bourgaux [France] ; Michel Prudhomme [France] ; Claire Philippe [France] ; Sophie Bravo [France] ; Jean Christophe Boyer [France] ; Lucile Canterel-Thouennon [France] ; Graham Roy Taylor [Australie] ; Arthur Hsu [Australie] ; Jean Marc Pascussi [France] ; Frédéric Hollande [France, Australie] ; Julie Pannequin [France]

Source :

Gut [ 0017-5749 ] ; 2016.

RBID : PMC:5595103

Descripteurs français

KwdFr :
- ARN tumoral (analyse), Aldehyde dehydrogenase (génétique), Aldehyde dehydrogenase (métabolisme), Analyse de séquence d'ARN, Animaux, Antigènes CD44 (génétique), Antigènes CD44 (métabolisme), Antinéoplasiques (métabolisme), Auto-renouvellement cellulaire, Cellules cancéreuses en culture, Cellules souches tumorales (enzymologie), Cellules souches tumorales (physiologie), Cellules tumorales circulantes (métabolisme), Culture primaire de cellules, Différenciation cellulaire, Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (métabolisme), Humains, Inactivation métabolique (génétique), Phénotype, Régulation positive, Résistance aux médicaments antinéoplasiques (génétique), Souris, Transplantation tumorale, Tumeurs colorectales (anatomopathologie), Tumeurs colorectales (génétique), Tumeurs colorectales (sang), Tumeurs du foie (anatomopathologie), Tumeurs du foie (secondaire).
MESH :
- analyse : ARN tumoral.
- anatomopathologie : Tumeurs colorectales, Tumeurs du foie.
- enzymologie : Cellules souches tumorales.
- génétique : Aldehyde dehydrogenase, Antigènes CD44, Dipeptidyl peptidase 4, Inactivation métabolique, Résistance aux médicaments antinéoplasiques, Tumeurs colorectales.
- métabolisme : Aldehyde dehydrogenase, Antigènes CD44, Antinéoplasiques, Cellules tumorales circulantes, Dipeptidyl peptidase 4.
- physiologie : Cellules souches tumorales.
- sang : Tumeurs colorectales.
- secondaire : Tumeurs du foie.
- Analyse de séquence d'ARN, Animaux, Auto-renouvellement cellulaire, Cellules cancéreuses en culture, Culture primaire de cellules, Différenciation cellulaire, Humains, Phénotype, Régulation positive, Souris, Transplantation tumorale.

English descriptors

KwdEn :
- Aldehyde Dehydrogenase (genetics), Aldehyde Dehydrogenase (metabolism), Animals, Antigens, CD44 (genetics), Antigens, CD44 (metabolism), Antineoplastic Agents (metabolism), Cell Differentiation, Cell Self Renewal, Colorectal Neoplasms (blood), Colorectal Neoplasms (genetics), Colorectal Neoplasms (pathology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Drug Resistance, Neoplasm (genetics), Humans, Inactivation, Metabolic (genetics), Liver Neoplasms (pathology), Liver Neoplasms (secondary), Mice, Neoplasm Transplantation, Neoplastic Cells, Circulating (metabolism), Neoplastic Stem Cells (enzymology), Neoplastic Stem Cells (physiology), Phenotype, Primary Cell Culture, RNA, Neoplasm (analysis), Sequence Analysis, RNA, Tumor Cells, Cultured, Up-Regulation.
MESH :
- chemical , analysis : RNA, Neoplasm.
- chemical , genetics : Aldehyde Dehydrogenase, Antigens, CD44, Dipeptidyl Peptidase 4.
- chemical , metabolism : Aldehyde Dehydrogenase, Antigens, CD44, Antineoplastic Agents, Dipeptidyl Peptidase 4.
- blood : Colorectal Neoplasms.
- enzymology : Neoplastic Stem Cells.
- genetics : Colorectal Neoplasms, Drug Resistance, Neoplasm, Inactivation, Metabolic.
- metabolism : Neoplastic Cells, Circulating.
- pathology : Colorectal Neoplasms, Liver Neoplasms.
- physiology : Neoplastic Stem Cells.
- secondary : Liver Neoplasms.
- Animals, Cell Differentiation, Cell Self Renewal, Humans, Mice, Neoplasm Transplantation, Phenotype, Primary Cell Culture, Sequence Analysis, RNA, Tumor Cells, Cultured, Up-Regulation.

Abstract

Objective

Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.

Design

Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.

Results

Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo. Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds.

Conclusions

Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine.

Clinical Trial Registration

ClinicalTrial.gov NCT01577511.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595103

DOI: 10.1136/gutjnl-2016-311447
PubMed: 27456153
PubMed Central: 5595103

Affiliations:

Australie, France

Links to Exploration step

PMC:5595103

Le document en format XML

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<author><name sortKey="Rolland, Nathalie" sort="Rolland, Nathalie" uniqKey="Rolland N" first="Nathalie" last="Rolland">Nathalie Rolland</name>
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<author><name sortKey="Bourgaux, Jean Francois" sort="Bourgaux, Jean Francois" uniqKey="Bourgaux J" first="Jean François" last="Bourgaux">Jean François Bourgaux</name>
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<author><name sortKey="Bravo, Sophie" sort="Bravo, Sophie" uniqKey="Bravo S" first="Sophie" last="Bravo">Sophie Bravo</name>
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<author><name sortKey="Boyer, Jean Christophe" sort="Boyer, Jean Christophe" uniqKey="Boyer J" first="Jean Christophe" last="Boyer">Jean Christophe Boyer</name>
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<author><name sortKey="Canterel Thouennon, Lucile" sort="Canterel Thouennon, Lucile" uniqKey="Canterel Thouennon L" first="Lucile" last="Canterel-Thouennon">Lucile Canterel-Thouennon</name>
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<author><name sortKey="Taylor, Graham Roy" sort="Taylor, Graham Roy" uniqKey="Taylor G" first="Graham Roy" last="Taylor">Graham Roy Taylor</name>
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<author><name sortKey="Hsu, Arthur" sort="Hsu, Arthur" uniqKey="Hsu A" first="Arthur" last="Hsu">Arthur Hsu</name>
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<author><name sortKey="Pascussi, Jean Marc" sort="Pascussi, Jean Marc" uniqKey="Pascussi J" first="Jean Marc" last="Pascussi">Jean Marc Pascussi</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
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<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
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<author><name sortKey="Pannequin, Julie" sort="Pannequin, Julie" uniqKey="Pannequin J" first="Julie" last="Pannequin">Julie Pannequin</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
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<idno type="wicri:Area/Ncbi/Merge">003897</idno>
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<idno type="wicri:Area/Ncbi/Checkpoint">003897</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in <italic>ex vivo</italic>
 culture</title>
<author><name sortKey="Grillet, Fanny" sort="Grillet, Fanny" uniqKey="Grillet F" first="Fanny" last="Grillet">Fanny Grillet</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bayet, Elsa" sort="Bayet, Elsa" uniqKey="Bayet E" first="Elsa" last="Bayet">Elsa Bayet</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Villeronce, Olivia" sort="Villeronce, Olivia" uniqKey="Villeronce O" first="Olivia" last="Villeronce">Olivia Villeronce</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zappia, Luke" sort="Zappia, Luke" uniqKey="Zappia L" first="Luke" last="Zappia">Luke Zappia</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lagerqvist, Ebba Louise" sort="Lagerqvist, Ebba Louise" uniqKey="Lagerqvist E" first="Ebba Louise" last="Lagerqvist">Ebba Louise Lagerqvist</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lunke, Sebastian" sort="Lunke, Sebastian" uniqKey="Lunke S" first="Sebastian" last="Lunke">Sebastian Lunke</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Charafe Jauffret, Emmanuelle" sort="Charafe Jauffret, Emmanuelle" uniqKey="Charafe Jauffret E" first="Emmanuelle" last="Charafe-Jauffret">Emmanuelle Charafe-Jauffret</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Centre de Recherche en Cancérologie de Marseille, U1068 Inserm</institution>
,<addr-line>Marseille</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pham, Kym" sort="Pham, Kym" uniqKey="Pham K" first="Kym" last="Pham">Kym Pham</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af6"><institution>Center for Translational Pathology, The University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Molck, Christina" sort="Molck, Christina" uniqKey="Molck C" first="Christina" last="Molck">Christina Molck</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rolland, Nathalie" sort="Rolland, Nathalie" uniqKey="Rolland N" first="Nathalie" last="Rolland">Nathalie Rolland</name>
<affiliation wicri:level="1"><nlm:aff id="af7"><institution>Service d'anatomopathologie, CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bourgaux, Jean Francois" sort="Bourgaux, Jean Francois" uniqKey="Bourgaux J" first="Jean François" last="Bourgaux">Jean François Bourgaux</name>
<affiliation wicri:level="1"><nlm:aff id="af8"><institution>Service d'Hépato-Gastroentérologie, CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Prudhomme, Michel" sort="Prudhomme, Michel" uniqKey="Prudhomme M" first="Michel" last="Prudhomme">Michel Prudhomme</name>
<affiliation wicri:level="1"><nlm:aff id="af9"><institution>Service de Chirurgie Digestive, CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Philippe, Claire" sort="Philippe, Claire" uniqKey="Philippe C" first="Claire" last="Philippe">Claire Philippe</name>
<affiliation wicri:level="1"><nlm:aff id="af9"><institution>Service de Chirurgie Digestive, CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bravo, Sophie" sort="Bravo, Sophie" uniqKey="Bravo S" first="Sophie" last="Bravo">Sophie Bravo</name>
<affiliation wicri:level="1"><nlm:aff id="af10"><addr-line>Laboratoire de Biochimie</addr-line>
,<institution>CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boyer, Jean Christophe" sort="Boyer, Jean Christophe" uniqKey="Boyer J" first="Jean Christophe" last="Boyer">Jean Christophe Boyer</name>
<affiliation wicri:level="1"><nlm:aff id="af10"><addr-line>Laboratoire de Biochimie</addr-line>
,<institution>CHU Carémeau</institution>
,<addr-line>Nîmes</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Canterel Thouennon, Lucile" sort="Canterel Thouennon, Lucile" uniqKey="Canterel Thouennon L" first="Lucile" last="Canterel-Thouennon">Lucile Canterel-Thouennon</name>
<affiliation wicri:level="1"><nlm:aff id="af11"><institution>Plateforme MPCC—SIRIC Montpellier Cancer, IRCM</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Taylor, Graham Roy" sort="Taylor, Graham Roy" uniqKey="Taylor G" first="Graham Roy" last="Taylor">Graham Roy Taylor</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hsu, Arthur" sort="Hsu, Arthur" uniqKey="Hsu A" first="Arthur" last="Hsu">Arthur Hsu</name>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pascussi, Jean Marc" sort="Pascussi, Jean Marc" uniqKey="Pascussi J" first="Jean Marc" last="Pascussi">Jean Marc Pascussi</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Pathology</addr-line>
,<institution>University of Melbourne</institution>
,<addr-line>Parkville, Victoria</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pannequin, Julie" sort="Pannequin, Julie" uniqKey="Pannequin J" first="Julie" last="Pannequin">Julie Pannequin</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><institution>Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>Institut National de la Santé et de la Recherche Médicale, U661</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3"><institution>Université de Montpellier, UMR5203</institution>
,<addr-line>Montpellier</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Gut</title>
<idno type="ISSN">0017-5749</idno>
<idno type="eISSN">1468-3288</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aldehyde Dehydrogenase (genetics)</term>
<term>Aldehyde Dehydrogenase (metabolism)</term>
<term>Animals</term>
<term>Antigens, CD44 (genetics)</term>
<term>Antigens, CD44 (metabolism)</term>
<term>Antineoplastic Agents (metabolism)</term>
<term>Cell Differentiation</term>
<term>Cell Self Renewal</term>
<term>Colorectal Neoplasms (blood)</term>
<term>Colorectal Neoplasms (genetics)</term>
<term>Colorectal Neoplasms (pathology)</term>
<term>Dipeptidyl Peptidase 4 (genetics)</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Drug Resistance, Neoplasm (genetics)</term>
<term>Humans</term>
<term>Inactivation, Metabolic (genetics)</term>
<term>Liver Neoplasms (pathology)</term>
<term>Liver Neoplasms (secondary)</term>
<term>Mice</term>
<term>Neoplasm Transplantation</term>
<term>Neoplastic Cells, Circulating (metabolism)</term>
<term>Neoplastic Stem Cells (enzymology)</term>
<term>Neoplastic Stem Cells (physiology)</term>
<term>Phenotype</term>
<term>Primary Cell Culture</term>
<term>RNA, Neoplasm (analysis)</term>
<term>Sequence Analysis, RNA</term>
<term>Tumor Cells, Cultured</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN tumoral (analyse)</term>
<term>Aldehyde dehydrogenase (génétique)</term>
<term>Aldehyde dehydrogenase (métabolisme)</term>
<term>Analyse de séquence d'ARN</term>
<term>Animaux</term>
<term>Antigènes CD44 (génétique)</term>
<term>Antigènes CD44 (métabolisme)</term>
<term>Antinéoplasiques (métabolisme)</term>
<term>Auto-renouvellement cellulaire</term>
<term>Cellules cancéreuses en culture</term>
<term>Cellules souches tumorales (enzymologie)</term>
<term>Cellules souches tumorales (physiologie)</term>
<term>Cellules tumorales circulantes (métabolisme)</term>
<term>Culture primaire de cellules</term>
<term>Différenciation cellulaire</term>
<term>Dipeptidyl peptidase 4 (génétique)</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
<term>Humains</term>
<term>Inactivation métabolique (génétique)</term>
<term>Phénotype</term>
<term>Régulation positive</term>
<term>Résistance aux médicaments antinéoplasiques (génétique)</term>
<term>Souris</term>
<term>Transplantation tumorale</term>
<term>Tumeurs colorectales (anatomopathologie)</term>
<term>Tumeurs colorectales (génétique)</term>
<term>Tumeurs colorectales (sang)</term>
<term>Tumeurs du foie (anatomopathologie)</term>
<term>Tumeurs du foie (secondaire)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>RNA, Neoplasm</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Aldehyde Dehydrogenase</term>
<term>Antigens, CD44</term>
<term>Dipeptidyl Peptidase 4</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Aldehyde Dehydrogenase</term>
<term>Antigens, CD44</term>
<term>Antineoplastic Agents</term>
<term>Dipeptidyl Peptidase 4</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN tumoral</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs colorectales</term>
<term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Colorectal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Cellules souches tumorales</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Neoplastic Stem Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Colorectal Neoplasms</term>
<term>Drug Resistance, Neoplasm</term>
<term>Inactivation, Metabolic</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Aldehyde dehydrogenase</term>
<term>Antigènes CD44</term>
<term>Dipeptidyl peptidase 4</term>
<term>Inactivation métabolique</term>
<term>Résistance aux médicaments antinéoplasiques</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neoplastic Cells, Circulating</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Aldehyde dehydrogenase</term>
<term>Antigènes CD44</term>
<term>Antinéoplasiques</term>
<term>Cellules tumorales circulantes</term>
<term>Dipeptidyl peptidase 4</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Colorectal Neoplasms</term>
<term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules souches tumorales</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Neoplastic Stem Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Differentiation</term>
<term>Cell Self Renewal</term>
<term>Humans</term>
<term>Mice</term>
<term>Neoplasm Transplantation</term>
<term>Phenotype</term>
<term>Primary Cell Culture</term>
<term>Sequence Analysis, RNA</term>
<term>Tumor Cells, Cultured</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de séquence d'ARN</term>
<term>Animaux</term>
<term>Auto-renouvellement cellulaire</term>
<term>Cellules cancéreuses en culture</term>
<term>Culture primaire de cellules</term>
<term>Différenciation cellulaire</term>
<term>Humains</term>
<term>Phénotype</term>
<term>Régulation positive</term>
<term>Souris</term>
<term>Transplantation tumorale</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objective</title>
<p>Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.</p>
</sec>
<sec><title>Design</title>
<p>Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.</p>
</sec>
<sec><title>Results</title>
<p>Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both <italic>in vitro</italic>
 and <italic>in vivo</italic>
. Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds.</p>
</sec>
<sec><title>Conclusions</title>
<p>Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine.</p>
</sec>
<sec><title>Clinical Trial Registration</title>
<p>ClinicalTrial.gov NCT01577511.</p>
</sec>
</div>
</front>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Ach, T" uniqKey="Ach T">T Ach</name>
</author>
<author><name sortKey="Schwarz Furlan, S" uniqKey="Schwarz Furlan S">S Schwarz-Furlan</name>
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<author><name sortKey="Ach, S" uniqKey="Ach S">S Ach</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Toss, A" uniqKey="Toss A">A Toss</name>
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<author><name sortKey="Mu, Z" uniqKey="Mu Z">Z Mu</name>
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<author><name sortKey="Fernandez, S" uniqKey="Fernandez S">S Fernandez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gong, C" uniqKey="Gong C">C Gong</name>
</author>
<author><name sortKey="Liu, B" uniqKey="Liu B">B Liu</name>
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<author><name sortKey="Yao, Y" uniqKey="Yao Y">Y Yao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cayrefourcq, L" uniqKey="Cayrefourcq L">L Cayrefourcq</name>
</author>
<author><name sortKey="Mazard, T" uniqKey="Mazard T">T Mazard</name>
</author>
<author><name sortKey="Joosse, S" uniqKey="Joosse S">S Joosse</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
</country>
</list>
<tree><country name="France"><noRegion><name sortKey="Grillet, Fanny" sort="Grillet, Fanny" uniqKey="Grillet F" first="Fanny" last="Grillet">Fanny Grillet</name>
</noRegion>
<name sortKey="Bayet, Elsa" sort="Bayet, Elsa" uniqKey="Bayet E" first="Elsa" last="Bayet">Elsa Bayet</name>
<name sortKey="Bayet, Elsa" sort="Bayet, Elsa" uniqKey="Bayet E" first="Elsa" last="Bayet">Elsa Bayet</name>
<name sortKey="Bayet, Elsa" sort="Bayet, Elsa" uniqKey="Bayet E" first="Elsa" last="Bayet">Elsa Bayet</name>
<name sortKey="Bourgaux, Jean Francois" sort="Bourgaux, Jean Francois" uniqKey="Bourgaux J" first="Jean François" last="Bourgaux">Jean François Bourgaux</name>
<name sortKey="Boyer, Jean Christophe" sort="Boyer, Jean Christophe" uniqKey="Boyer J" first="Jean Christophe" last="Boyer">Jean Christophe Boyer</name>
<name sortKey="Bravo, Sophie" sort="Bravo, Sophie" uniqKey="Bravo S" first="Sophie" last="Bravo">Sophie Bravo</name>
<name sortKey="Canterel Thouennon, Lucile" sort="Canterel Thouennon, Lucile" uniqKey="Canterel Thouennon L" first="Lucile" last="Canterel-Thouennon">Lucile Canterel-Thouennon</name>
<name sortKey="Charafe Jauffret, Emmanuelle" sort="Charafe Jauffret, Emmanuelle" uniqKey="Charafe Jauffret E" first="Emmanuelle" last="Charafe-Jauffret">Emmanuelle Charafe-Jauffret</name>
<name sortKey="Grillet, Fanny" sort="Grillet, Fanny" uniqKey="Grillet F" first="Fanny" last="Grillet">Fanny Grillet</name>
<name sortKey="Grillet, Fanny" sort="Grillet, Fanny" uniqKey="Grillet F" first="Fanny" last="Grillet">Fanny Grillet</name>
<name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
<name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
<name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
<name sortKey="Lagerqvist, Ebba Louise" sort="Lagerqvist, Ebba Louise" uniqKey="Lagerqvist E" first="Ebba Louise" last="Lagerqvist">Ebba Louise Lagerqvist</name>
<name sortKey="Lagerqvist, Ebba Louise" sort="Lagerqvist, Ebba Louise" uniqKey="Lagerqvist E" first="Ebba Louise" last="Lagerqvist">Ebba Louise Lagerqvist</name>
<name sortKey="Lagerqvist, Ebba Louise" sort="Lagerqvist, Ebba Louise" uniqKey="Lagerqvist E" first="Ebba Louise" last="Lagerqvist">Ebba Louise Lagerqvist</name>
<name sortKey="Pannequin, Julie" sort="Pannequin, Julie" uniqKey="Pannequin J" first="Julie" last="Pannequin">Julie Pannequin</name>
<name sortKey="Pannequin, Julie" sort="Pannequin, Julie" uniqKey="Pannequin J" first="Julie" last="Pannequin">Julie Pannequin</name>
<name sortKey="Pannequin, Julie" sort="Pannequin, Julie" uniqKey="Pannequin J" first="Julie" last="Pannequin">Julie Pannequin</name>
<name sortKey="Pascussi, Jean Marc" sort="Pascussi, Jean Marc" uniqKey="Pascussi J" first="Jean Marc" last="Pascussi">Jean Marc Pascussi</name>
<name sortKey="Pascussi, Jean Marc" sort="Pascussi, Jean Marc" uniqKey="Pascussi J" first="Jean Marc" last="Pascussi">Jean Marc Pascussi</name>
<name sortKey="Pascussi, Jean Marc" sort="Pascussi, Jean Marc" uniqKey="Pascussi J" first="Jean Marc" last="Pascussi">Jean Marc Pascussi</name>
<name sortKey="Philippe, Claire" sort="Philippe, Claire" uniqKey="Philippe C" first="Claire" last="Philippe">Claire Philippe</name>
<name sortKey="Prudhomme, Michel" sort="Prudhomme, Michel" uniqKey="Prudhomme M" first="Michel" last="Prudhomme">Michel Prudhomme</name>
<name sortKey="Rolland, Nathalie" sort="Rolland, Nathalie" uniqKey="Rolland N" first="Nathalie" last="Rolland">Nathalie Rolland</name>
<name sortKey="Villeronce, Olivia" sort="Villeronce, Olivia" uniqKey="Villeronce O" first="Olivia" last="Villeronce">Olivia Villeronce</name>
<name sortKey="Villeronce, Olivia" sort="Villeronce, Olivia" uniqKey="Villeronce O" first="Olivia" last="Villeronce">Olivia Villeronce</name>
<name sortKey="Villeronce, Olivia" sort="Villeronce, Olivia" uniqKey="Villeronce O" first="Olivia" last="Villeronce">Olivia Villeronce</name>
</country>
<country name="Australie"><noRegion><name sortKey="Zappia, Luke" sort="Zappia, Luke" uniqKey="Zappia L" first="Luke" last="Zappia">Luke Zappia</name>
</noRegion>
<name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name>
<name sortKey="Hsu, Arthur" sort="Hsu, Arthur" uniqKey="Hsu A" first="Arthur" last="Hsu">Arthur Hsu</name>
<name sortKey="Lunke, Sebastian" sort="Lunke, Sebastian" uniqKey="Lunke S" first="Sebastian" last="Lunke">Sebastian Lunke</name>
<name sortKey="Molck, Christina" sort="Molck, Christina" uniqKey="Molck C" first="Christina" last="Molck">Christina Molck</name>
<name sortKey="Pham, Kym" sort="Pham, Kym" uniqKey="Pham K" first="Kym" last="Pham">Kym Pham</name>
<name sortKey="Pham, Kym" sort="Pham, Kym" uniqKey="Pham K" first="Kym" last="Pham">Kym Pham</name>
<name sortKey="Taylor, Graham Roy" sort="Taylor, Graham Roy" uniqKey="Taylor G" first="Graham Roy" last="Taylor">Graham Roy Taylor</name>
</country>
</tree>
</affiliations>
</record>

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   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Ncbi
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   |type=    RBID
   |clé=     PMC:5595103
   |texte=   Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture
}}

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Serveur d'exploration sur les relations entre la France et l'Australie

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture

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	Serveur d'exploration sur les relations entre la France et l'Australie
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