Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer

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dc.citation.articleNumbereabg5283en_US
dc.citation.issueNumber30en_US
dc.citation.journalTitleScience Advancesen_US
dc.citation.volumeNumber7en_US
dc.contributor.authorSaha, Biswajiten_US
dc.contributor.authorMathur, Tanmayen_US
dc.contributor.authorTronolone, James J.en_US
dc.contributor.authorChokshi, Mithilen_US
dc.contributor.authorLokhande, Giriraj K.en_US
dc.contributor.authorSelahi, Amiralien_US
dc.contributor.authorGaharwar, Akhilesh K.en_US
dc.contributor.authorAfshar-Kharghan, Vahiden_US
dc.contributor.authorSood, Anil K.en_US
dc.contributor.authorBao, Gangen_US
dc.contributor.authorJain, Abhisheken_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2021-08-05T15:51:53Zen_US
dc.date.available2021-08-05T15:51:53Zen_US
dc.date.issued2021en_US
dc.description.abstractPlatelets extravasate from the circulation into tumor microenvironment, enable metastasis, and confer resistance to chemotherapy in several cancers. Therefore, arresting tumor-platelet cross-talk with effective and atoxic antiplatelet agents in combination with anticancer drugs may serve as an effective cancer treatment strategy. To test this concept, we create an ovarian tumor microenvironment chip (OTME-Chip) that consists of a platelet-perfused tumor microenvironment and which recapitulates platelet extravasation and its consequences. By including gene-edited tumors and RNA sequencing, this organ-on-chip revealed that platelets and tumors interact through glycoprotein VI (GPVI) and tumor galectin-3 under shear. Last, as proof of principle of a clinical trial, we showed that a GPVI inhibitor, Revacept, impairs metastatic potential and improves chemotherapy. Since GPVI is an antithrombotic target that does not impair hemostasis, it represents a safe cancer therapeutic. We propose that OTME-Chip could be deployed to study other vascular and hematological targets in cancer. A tumor microenvironment chip reveals how platelets may fuel cancer metastasis and chemoresistance and unravels a new treatment. A tumor microenvironment chip reveals how platelets may fuel cancer metastasis and chemoresistance and unravels a new treatment.en_US
dc.identifier.citationSaha, Biswajit, Mathur, Tanmay, Tronolone, James J., et al.. "Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer." <i>Science Advances,</i> 7, no. 30 (2021) AAAS: https://doi.org/10.1126/sciadv.abg5283.en_US
dc.identifier.digitaleabg5283-fullen_US
dc.identifier.doihttps://doi.org/10.1126/sciadv.abg5283en_US
dc.identifier.urihttps://hdl.handle.net/1911/111136en_US
dc.language.isoengen_US
dc.publisherAAASen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleHuman tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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