P1639: platelet-educated cancer cells overexpress fibronectin as well as different glycosyltransferases.

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Cancer-associated thrombosis, also known as Trousseau’s syndrome, is the second most common cause of death among cancer patients, after the disease itself. Indeed, venous thrombosis is 4 to 7 times more common in these patients. Many factors contribute to this hypercoagulable state, but one of them is the ability of tumor cells to activate platelets and induce their aggregation (TCIPA). This phenomenon of cancer cell-educated platelets is associated with higher metastatic potential. Nevertheless, our team demonstrated the opposite concept in 2019 in which platelets educate cancer cells by transferring material to them. Aims: In this study, we aim to better understand how platelets facilitate metastasis formation during their interaction with tumor cells. Methods: Changes in the expression of 43 glycosyltransferases (GT) families as well as 160 genes involved in inflammation and metastasis were analyzed by RT-qPCR in digestive cancer cell lines following their interaction with platelets. Functional tests (transwell migration and invasion assay, wound healing assay,...) and holo-tomographic microscopy were used to understand the role of the identified genes of interest in glycosylation and formation of metastasis. Results: As platelets have been previously shown to initiate and extend glycosylation of extracellular molecules, we thought they could modify the glycosylation of cancer-cell expressed proteins during their interaction. We first demonstrated, however, that platelets by themselves express very few glycosyltransferases with limited functional activities. Using holo-tomographic microscopy we observed that tumor cells that interacted with platelets have a higher dry mass than before their interaction. This may reflect a transfer of material in a process described as platelet-educated cancer cells. Platelet-educated cancer cells are also able to proliferate significantly more than cancer cells, indicating a selective advantage in the transfer of material from platelets to the cancer cells. We screened 43 different GT families in tumor cells educated or not by platelets. Three families of GT were overexpressed (B3GNT, GCNT, C1GALTC1) respectively by 200, 100 and 60% in tumor cells after their interaction with platelets. These GT significantly increased the potential glycosylation of proteins in cancer cells. Interestingly, we also found that out of 160 genes involved in inflammation and metastasis, mRNA coding for the glycoprotein fibronectin (FN1) was overexpressed by 160% in platelet-educated tumor cells. In tumor cells, knocking down FN1 significantly affects the migration and proliferation of the cells. Summary/Conclusion: We concluded that the interaction between tumor cells and platelets can induce the over-expression of different glycosyltransferases and FN1 in tumor cells. This education may have an impact on cancer development and metastasis. Keywords: Cancer, Glycosylation, Platelet