Microfluidic chip model for drug development against chemoresistance
2021
Texas A&M University, College Station, USA
The leakage of platelets from the vessels into the microenvironment of tumors is associated with increased proliferation of cancer cells, as well as the formation of metastases and leads to chemoresistance in several types of cancer. The present study presents an ovarian-tumor-microenvironment-chip model (OTME-chip) specifically developed for the recapitulation of platelet extrusion and analysis of tumor-cell interaction. In addition to the tumor cell chamber, the microfluidic model consists of a complex 3D hydrogel chamber that reflects the tumor microenvironment and platelet flow in the vessels. By means of gene editing and RNA sequencing analysis, it was observed that the platelets bind to the circulating tumor surface glycoprotein galectin-3 under vascular shear stress via glycoprotein VI (GPVI), which could promote the growth of the cancer cells. Furthermore, the effect of the antiplatelet aggregation drug Revacept, which has already been successfully tested in phase-1 clinical trials in atherosclerosis and stroke, on platelet-tumor-microenvironment interactions was investigated. The bonds between GPVI and galectin-3 were significantly reduced by treatment. In addition, a decrease in proliferation and invasion of tumor cells into the surrounding microtissue was observed. This suggests that GPVI inhibition can also prevent the consequences of a cancer-causing interaction between the platelets and the tumor protein galectin-3 and could reduce the formation of chemoresistance. Based on the results, the OTME-chip, in combination with gene editing and RNA sequence analysis, proves to be a suitable model for analyzing the interaction of cancer cells with cells of the vascular system, as well as their consequences for the tumor microenvironment. The chip model can also be helpful for the development of (concomitant) cancer drugs.
Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
Abhishek Jain
Added on: 08-22-2022
[1] https://www.science.org/doi/10.1126/sciadv.abg5283
