Morris Kenise, Masri Salah, Schnoor Brian, Papa Anne-Laure
Department of Biomedical Engineering, School of Engineering and Applied Science, The George Washington University, Washington, DC, 20052, USA.
Sci Rep. 2025 Mar 5;15(1):7750. doi: 10.1038/s41598-024-79280-8.
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.
血小板与癌细胞的相互作用在转移过程中起着重要作用。事实上，它们通过大量受体相互作用，包括整合素（如αIIbβ3和αvβ3），钙对于它们的稳定性和功能都至关重要。此外，钙在凝血级联反应中有重要作用，而钙水平变化对转移扩散和癌症相关血栓形成的影响尚未完全明确。相当一部分癌症患者患有高钙血症，且预后较差。我们推测钙水平对于通过整合素介导的血小板与癌细胞的相互作用很重要，因此可以利用这一点来破坏血小板对转移过程 的支持作用。在本研究中，我们在调节钙水平的同时，评估了血小板 和癌细胞上整合素αIIbβ3和αvβ3 的检测、血小板功能以及参与血小板功能的各自受体。还评估了钙水平对体外血小板 -癌细胞相互作用和癌细胞侵袭的影响。我们的数据表明，钙水平会影响表面整合素以及参与血小板 -癌细胞相互作用的受体。此外，钙水平会显著影响血小板的激活和聚集。在我们的实验情况下，钙耗竭会调节血小板与MDA - MB - 231乳腺癌细胞的相互作用，而高钙环境则不影响这种相互作用。同时，在有血小板存在的情况下，高钙血症会导致MDA - MB - 231和A549细胞的癌细胞侵袭增强。因此，本研究更深入地了解了与钙的作用以及由整合素介导的血小板 -癌细胞相互作用相关的动态过程。
