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 anti-platelet 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 anti-thrombotic 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.

Automated summary

Platelets play a crucial role in the tumor microenvironment, and inhibiting the interaction between platelets and tumor cells may be an effective cancer treatment strategy. Using an ovarian tumor microenvironment chip (OTME-Chip), it was revealed that platelets and tumors interact through GPVI and tumor galectin-3, and inhibiting GPVI could reduce metastatic potential and enhance chemotherapy efficacy. Leveraging the findings from this study, the OTME-Chip could be utilized to explore other vascular and hematological targets in cancer research.