Calcium levels modulate platelet function, platelet-cancer cell interaction, and cancer cell invasion

Platelet-cancer cell interactions play a significant role in metastasis. Indeed, they interact via a plethora of receptors, including integrins (e.g. ⍺IIbβ3 and ⍺vβ3), and calcium is essential for both their stability and function. Additionally, calcium plays a significant role in the coagulation cascade, and the implication of calcium level changes on metastatic dissemination and cancer-associated thrombosis are not fully understood. A significant proportion of cancer patients suffer from hypercalcemia and have a worse prognosis. We hypothesized that calcium levels are important for platelet-cancer cell interactions that are mediated via integrins, thus this can be leveraged to disrupt platelet support to the metastatic process. In this study, we assessed the detection of integrins ⍺IIbβ3 and ⍺vβ3 on platelets and cancer cells, platelet function, and the respective receptors implicated in platelet function, while modulating calcium levels. The effect of calcium levels on platelet-cancer cell interactions and cancer cell invasion in vitro was also assessed. Our data demonstrates that calcium levels affect surface integrins, and receptors involved in platelet-cancer cell interactions. In addition, calcium levels significantly affect platelet activation and aggregation. In our experimental scenarios, calcium depletion modulates platelet-cancer cell interaction with MDA-MB-231 breast cancer cells, while hypercalcemic environments did not affect interaction. Meanwhile, hypercalcemia leads to enhanced cancer cell invasion for both MDA-MB-231 and A549 cells in the presence of platelets. Thus, this study provides a greater understanding of the dynamics associated with the effects of calcium and platelet-cancer cell interactions mediated by integrins.