VWF Mediates Platelet Activation and Secretion to Promote Osteosarcoma Metastasis

[Background] As a multimer protein that mediates the adhesion of platelets to vascular surface, VWF has been found to participate in tumor metastasis, and may also be involved in the interaction between platelets and tumor cells. We observed in our clinical studies that the expression of VWF in lung metastatic osteosarcoma tumor is significantly higher than that of in primary osteosarcoma. Based on these observations, we speculate that VWF and platelets may contribute to promoting osteosarcoma metastasis. Thus, this study is to explore the effects of VWF-mediated platelet activation and secretion on the migration and invasion ability of SAOS2 cells with VWF-expressing osteosarcoma cell line SAOS2 as a model, as well as the inhibition of the interaction between VWF and platelets by specific antibodies.

[Methods] SAOS2 cells were stimulated with inflammatory factor PMA and resulted in increased expression of vWF. Then the adhesion of labeled platelets to SAOS2 cells was evaluated under static and flow conditions, respectively. The above processes were intervened with SZ-2(anti-GPIb), SZ-123(anti-VWF) and AVW3 (anti-VWF) mAbs which specifically blocked the vWF-GPIbα pathway. Transwell assay was used to explore the effect of vWF-mediated migration and invasion ability of SAOS2 cells. PDGF-BB, TGF-β and VEGF that could be secreted by platelets to promote tumor cells growth in the co-culture system of platelets and SAOS2 cells were detected by ELISA.

[Results] Under static and flow conditions, SAOS2 cells treated with PMA exhibited significantly higher platelets-adhesion capacity compared to the cells untreated with PMA, and the adhesion could be partially inhibited by SZ-2 and AVW3 mAbs. Furthermore, platelets significantly promoted the migration and invasion ability of SAOS2 cells, and PDGF-BB and TGF-β secreted by platelets were also increased in these processes. Both of SZ-2 and AVW3 mAbs partially decreased the migration and invasion ability of SAOS2 cells.

[Conclusions] vWF were expressed highly in some kind of non-endothelial origin cancer cells, such as SAOS2, which mediates platelet activation and secreting factors such as PDGF-BB and TGF-β to promote tumor cells growth. Activated platelets have a significant promoted effect on the migration and invasion ability of SAOS2 cells and this process can be inhibited by antibodies that specifically block the pathway of VWF-GPIbα.