A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis
Identifieur interne : 000855 ( Main/Exploration ); précédent : 000854; suivant : 000856A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis
Auteurs : Ai Takemoto [Japon] ; Mina Okitaka [Japon] ; Satoshi Takagi [Japon] ; Miho Takami [Japon] ; Shigeo Sato [Japon] ; Makoto Nishio [Japon] ; Sakae Okumura [Japon] ; Naoya Fujita [Japon]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets.
Url:
DOI: 10.1038/srep42186
PubMed: 28176852
PubMed Central: 5297242
Affiliations:
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Takami, Miho" sort="Takami, Miho" uniqKey="Takami M" first="Miho" last="Takami">Miho Takami</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sato, Shigeo" sort="Sato, Shigeo" uniqKey="Sato S" first="Shigeo" last="Sato">Shigeo Sato</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country 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strict</wicri:regionArea></affiliation></author><author><name sortKey="Fujita, Naoya" sort="Fujita, Naoya" uniqKey="Fujita N" first="Naoya" last="Fujita">Naoya Fujita</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo</institution>, Kashiwa, Chiba 277-8561,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno 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type="wicri:Area/Main/Exploration">000855</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis</title><author><name sortKey="Takemoto, Ai" sort="Takemoto, Ai" uniqKey="Takemoto A" first="Ai" last="Takemoto">Ai Takemoto</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Okitaka, Mina" sort="Okitaka, Mina" uniqKey="Okitaka M" first="Mina" last="Okitaka">Mina Okitaka</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo</institution>, Kashiwa, Chiba 277-8561,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Takagi, Satoshi" sort="Takagi, Satoshi" uniqKey="Takagi S" first="Satoshi" last="Takagi">Satoshi Takagi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Takami, Miho" sort="Takami, Miho" uniqKey="Takami M" first="Miho" last="Takami">Miho Takami</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sato, Shigeo" sort="Sato, Shigeo" uniqKey="Sato S" first="Shigeo" last="Sato">Shigeo Sato</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nishio, Makoto" sort="Nishio, Makoto" uniqKey="Nishio M" first="Makoto" last="Nishio">Makoto Nishio</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Okumura, Sakae" sort="Okumura, Sakae" uniqKey="Okumura S" first="Sakae" last="Okumura">Sakae Okumura</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fujita, Naoya" sort="Fujita, Naoya" uniqKey="Fujita N" first="Naoya" last="Fujita">Naoya Fujita</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research</institution>, Tokyo 135-8550,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo</institution>, Kashiwa, Chiba 277-8561,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets. <italic>In vitro</italic> and <italic>in vivo</italic> analyses revealed that podoplanin-mediated EMT resulted in increased invasiveness and extravasation of tumour cells. Treatment of mice with a TGF-β-neutralizing antibody statistically suppressed podoplanin-mediated distant metastasis <italic>in vivo</italic>, suggesting that podoplanin promoted haematogenous metastasis in part by releasing TGF-β from platelets that was essential for EMT of tumour cells. Therefore, our findings suggested that blocking the TGF-β signalling pathway might be a promising strategy for suppressing podoplanin-mediated haematogenous metastasis <italic>in vivo</italic>.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gay, L J" uniqKey="Gay L">L. J. Gay</name></author><author><name sortKey="Felding Habermann, B" uniqKey="Felding Habermann B">B. Felding-Habermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bambace, N M" uniqKey="Bambace N">N. M. Bambace</name></author><author><name sortKey="Holmes, C E" uniqKey="Holmes C">C. E. 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Watson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Takemoto, Ai" sort="Takemoto, Ai" uniqKey="Takemoto A" first="Ai" last="Takemoto">Ai Takemoto</name></noRegion><name sortKey="Fujita, Naoya" sort="Fujita, Naoya" uniqKey="Fujita N" first="Naoya" last="Fujita">Naoya Fujita</name><name sortKey="Fujita, Naoya" sort="Fujita, Naoya" uniqKey="Fujita N" first="Naoya" last="Fujita">Naoya Fujita</name><name sortKey="Nishio, Makoto" sort="Nishio, Makoto" uniqKey="Nishio M" first="Makoto" last="Nishio">Makoto Nishio</name><name sortKey="Okitaka, Mina" sort="Okitaka, Mina" uniqKey="Okitaka M" first="Mina" last="Okitaka">Mina Okitaka</name><name sortKey="Okitaka, Mina" sort="Okitaka, Mina" uniqKey="Okitaka M" first="Mina" last="Okitaka">Mina Okitaka</name><name sortKey="Okumura, Sakae" sort="Okumura, Sakae" uniqKey="Okumura S" first="Sakae" last="Okumura">Sakae Okumura</name><name sortKey="Sato, Shigeo" sort="Sato, Shigeo" uniqKey="Sato S" first="Shigeo" last="Sato">Shigeo Sato</name><name sortKey="Takagi, Satoshi" sort="Takagi, Satoshi" uniqKey="Takagi S" first="Satoshi" last="Takagi">Satoshi Takagi</name><name sortKey="Takami, Miho" sort="Takami, Miho" uniqKey="Takami M" first="Miho" last="Takami">Miho Takami</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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