Platelet-induced inhibition of tumor cell growth

Background: Previous studies have suggested that platelets play a role in hematogenous metastasis of cancer cells by enhancing their survival in and extravasation from the bloodstream. We initiated studies to determine the effect of platelets on the proliferation of tumor cells. Methods: Intact platelets or platelet subfractions were prepared and used for co-culture with various tumor cell lines of different major histocompatibility complex (MHC) backgrounds. Proliferation of tumor cells was monitored using a colorigenic method; flow cytometry was used to measure apoptosis or the cell cycle in L1210 cells. Results: Co-culture of platelets with tumor cells inhibited proliferation of tumor cells in an MHC-independent manner; soluble factors released from platelets as well as physical contact between platelets and tumor cells were involved. Cell-cycle analysis showed that platelets inhibited proliferation mainly through arrest of the cell cycle and inhibition of DNA synthesis. Neither cytotoxicity nor apoptosis mechanisms dominate in the platelet-induced inhibition of tumor cell proliferation. Conclusion: We observed that murine platelets inhibit growth of tumor cells in vitro in an MHC-I-independent way, and this inhibition is not limited to specific tumor types, nor is it dependent on cytotoxicity or apoptotic pathways; rather it relies on impairment of the cell cycle.