Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis
Identifieur interne : 006307 ( Main/Exploration ); précédent : 006306; suivant : 006308Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis
Auteurs : Johanna Lahdenranta ; Jeroen Hagendoorn ; Timothy P. Padera ; Tohru Hoshida ; Gregory Nelson ; Satoshi Kashiwagi ; Rakesh K. Jain ; Dai FukumuraSource :
- Cancer research [ 0008-5472 ] ; 2009.
Abstract
Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system.
Url:
DOI: 10.1158/0008-5472.CAN-08-4051
PubMed: 19318557
PubMed Central: 2670480
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 002836
- to stream Pmc, to step Curation: 002835
- to stream Pmc, to step Checkpoint: 003751
- to stream Ncbi, to step Merge: 003323
- to stream Ncbi, to step Curation: 003323
- to stream Ncbi, to step Checkpoint: 003323
- to stream Main, to step Merge: 006383
- to stream Main, to step Curation: 006307
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis</title>
<author><name sortKey="Lahdenranta, Johanna" sort="Lahdenranta, Johanna" uniqKey="Lahdenranta J" first="Johanna" last="Lahdenranta">Johanna Lahdenranta</name>
</author>
<author><name sortKey="Hagendoorn, Jeroen" sort="Hagendoorn, Jeroen" uniqKey="Hagendoorn J" first="Jeroen" last="Hagendoorn">Jeroen Hagendoorn</name>
</author>
<author><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name>
</author>
<author><name sortKey="Hoshida, Tohru" sort="Hoshida, Tohru" uniqKey="Hoshida T" first="Tohru" last="Hoshida">Tohru Hoshida</name>
</author>
<author><name sortKey="Nelson, Gregory" sort="Nelson, Gregory" uniqKey="Nelson G" first="Gregory" last="Nelson">Gregory Nelson</name>
</author>
<author><name sortKey="Kashiwagi, Satoshi" sort="Kashiwagi, Satoshi" uniqKey="Kashiwagi S" first="Satoshi" last="Kashiwagi">Satoshi Kashiwagi</name>
</author>
<author><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name>
</author>
<author><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">19318557</idno>
<idno type="pmc">2670480</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670480</idno>
<idno type="RBID">PMC:2670480</idno>
<idno type="doi">10.1158/0008-5472.CAN-08-4051</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">002836</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002836</idno>
<idno type="wicri:Area/Pmc/Curation">002835</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002835</idno>
<idno type="wicri:Area/Pmc/Checkpoint">003751</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003751</idno>
<idno type="wicri:Area/Ncbi/Merge">003323</idno>
<idno type="wicri:Area/Ncbi/Curation">003323</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003323</idno>
<idno type="wicri:doubleKey">0008-5472:2009:Lahdenranta J:endothelial:nitric:oxide</idno>
<idno type="wicri:Area/Main/Merge">006383</idno>
<idno type="wicri:Area/Main/Curation">006307</idno>
<idno type="wicri:Area/Main/Exploration">006307</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis</title>
<author><name sortKey="Lahdenranta, Johanna" sort="Lahdenranta, Johanna" uniqKey="Lahdenranta J" first="Johanna" last="Lahdenranta">Johanna Lahdenranta</name>
</author>
<author><name sortKey="Hagendoorn, Jeroen" sort="Hagendoorn, Jeroen" uniqKey="Hagendoorn J" first="Jeroen" last="Hagendoorn">Jeroen Hagendoorn</name>
</author>
<author><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name>
</author>
<author><name sortKey="Hoshida, Tohru" sort="Hoshida, Tohru" uniqKey="Hoshida T" first="Tohru" last="Hoshida">Tohru Hoshida</name>
</author>
<author><name sortKey="Nelson, Gregory" sort="Nelson, Gregory" uniqKey="Nelson G" first="Gregory" last="Nelson">Gregory Nelson</name>
</author>
<author><name sortKey="Kashiwagi, Satoshi" sort="Kashiwagi, Satoshi" uniqKey="Kashiwagi S" first="Satoshi" last="Kashiwagi">Satoshi Kashiwagi</name>
</author>
<author><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name>
</author>
<author><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name>
</author>
</analytic>
<series><title level="j">Cancer research</title>
<idno type="ISSN">0008-5472</idno>
<idno type="eISSN">1538-7445</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P2">Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system.</p>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name>
<name sortKey="Hagendoorn, Jeroen" sort="Hagendoorn, Jeroen" uniqKey="Hagendoorn J" first="Jeroen" last="Hagendoorn">Jeroen Hagendoorn</name>
<name sortKey="Hoshida, Tohru" sort="Hoshida, Tohru" uniqKey="Hoshida T" first="Tohru" last="Hoshida">Tohru Hoshida</name>
<name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name>
<name sortKey="Kashiwagi, Satoshi" sort="Kashiwagi, Satoshi" uniqKey="Kashiwagi S" first="Satoshi" last="Kashiwagi">Satoshi Kashiwagi</name>
<name sortKey="Lahdenranta, Johanna" sort="Lahdenranta, Johanna" uniqKey="Lahdenranta J" first="Johanna" last="Lahdenranta">Johanna Lahdenranta</name>
<name sortKey="Nelson, Gregory" sort="Nelson, Gregory" uniqKey="Nelson G" first="Gregory" last="Nelson">Gregory Nelson</name>
<name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name>
</noCountry>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 006307 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 006307 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:2670480 |texte= Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:19318557" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
This area was generated with Dilib version V0.6.31. |