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

Platelets 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 effec...

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Autores principales: Saha, Biswajit, Mathur, Tanmay, Tronolone, James J., Chokshi, Mithil, Lokhande, Giriraj K., Selahi, Amirali, Gaharwar, Akhilesh K., Afshar-Kharghan, Vahid, Sood, Anil K., Bao, Gang, Jain, Abhishek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294767/
https://www.ncbi.nlm.nih.gov/pubmed/34290095
http://dx.doi.org/10.1126/sciadv.abg5283
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author Saha, Biswajit
Mathur, Tanmay
Tronolone, James J.
Chokshi, Mithil
Lokhande, Giriraj K.
Selahi, Amirali
Gaharwar, Akhilesh K.
Afshar-Kharghan, Vahid
Sood, Anil K.
Bao, Gang
Jain, Abhishek
author_facet Saha, Biswajit
Mathur, Tanmay
Tronolone, James J.
Chokshi, Mithil
Lokhande, Giriraj K.
Selahi, Amirali
Gaharwar, Akhilesh K.
Afshar-Kharghan, Vahid
Sood, Anil K.
Bao, Gang
Jain, Abhishek
author_sort Saha, Biswajit
collection PubMed
description Platelets 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.
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spelling pubmed-82947672021-08-03 Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer Saha, Biswajit Mathur, Tanmay Tronolone, James J. Chokshi, Mithil Lokhande, Giriraj K. Selahi, Amirali Gaharwar, Akhilesh K. Afshar-Kharghan, Vahid Sood, Anil K. Bao, Gang Jain, Abhishek Sci Adv Research Articles Platelets 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. American Association for the Advancement of Science 2021-07-21 /pmc/articles/PMC8294767/ /pubmed/34290095 http://dx.doi.org/10.1126/sciadv.abg5283 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Saha, Biswajit
Mathur, Tanmay
Tronolone, James J.
Chokshi, Mithil
Lokhande, Giriraj K.
Selahi, Amirali
Gaharwar, Akhilesh K.
Afshar-Kharghan, Vahid
Sood, Anil K.
Bao, Gang
Jain, Abhishek
Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title_full Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title_fullStr Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title_full_unstemmed Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title_short Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
title_sort human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294767/
https://www.ncbi.nlm.nih.gov/pubmed/34290095
http://dx.doi.org/10.1126/sciadv.abg5283
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