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.
© 2025. The Author(s).

Lyophilized platelets have been explored as a potential hemostatic agent due to their long-term ambient storage capabilities that make them readily available in various scenarios. Additionally, their high biocompatibility and the key role of platelet interactions in various clinical conditions make them a promising platform for drug delivery. To explore these applications and for wider clinical deployment, the interactions between lyophilized platelets and fresh platelets must be examined. This project characterized receptor expression on the lyophilized platelet surface and their ability to bind fibrinogen using flow cytometry. The effect of lyophilized platelets on aggregation of unaltered platelets was assessed using light transmission aggregometry while the effect on adhesion was evaluated using static and microfluidic assays. Lyophilized platelets maintained significant levels of GPIIb and GPVI receptors on their surface, though the expression was reduced from fresh platelets. Additionally, lyophilized platelets maintained GPIb expression similar to fresh platelets. Furthermore, 15.8% of the lyophilized platelets exhibited the active conformation of the GPIIb/IIIa receptor, indicating a significant increase over fresh platelets. Lyophilized platelets also exhibited an increase in exposed phosphatidylserine and fibrinogen binding. Despite the effect of lyophilized platelets in promoting the adhesion of fresh platelets on a collagen-coated surface, their net effect was inhibitory on platelet aggregation. This study demonstrates that lyophilized platelets can have paradoxical effects on platelet adhesion and aggregation, which could have an impact for clinical applications. Detailed characterization and engineering of these effects will be important for their continued development as a drug delivery platform.
Copyright © 2022 Schnoor and Papa.