OvCa-Chip: A New Organ-on-a-Chip Experimental Model to Dissect Platelet and Vascular (dys)Function in Ovarian Cancer
On Sunday, Abhishek Jain, Ph.D., of Texas A&M University in College Station, TX, presented results on OvCa-Chip, an ovarian tumor-vessel-blood-flow integrated in vitro biosystem, with the intent of evaluating critical platelet-medicated processes in ovarian cancer. What is known is that platelets migrate from the bloodstream into tumor microenvironments, supporting their growth. However, the full understanding of transendothelial platelet extravasation in cancer remains limited.
Jain had hypothesized that tumor cells release signals that result in nearby vascular endothelium losing barrier integrity, following which platelets extravasate into the tumor. Additionally, platelets interact with tumor Galectin-3 through their GPVI receptors, resulting in tumor proliferation.
The OvCa-Chip revealed that tumor-released factors resulted in activation of vascular endotholium through the Src kinase pathway, which eventually downregulated transcription factor vascular endothelial protein tyrosine phosphatase (VE-PTP) and inhibited formation of the VE-cadherin–β-catenin complex, which is crucial for endothelial barriers. Platelets transmigrated into tumors via communication with endothelial Tie-2, Pyk-1, and Rac-1 and, post extravasation, interacted with tumor Galectin-3 via GPVI, which triggered tumor growth and metastasis. Finally, they showed that statins and antiplatelet drugs can effectively arrest platelet–tumor contact and its consequences. This led to the conclusion of Jain that OvCa-Chip should be considered as a platform to model platelet and vascular function in cancer and new therapeutics.
Read the full abstract here.