Clinical Significance and Roles in Angiogenesis of Circulating Microparticles in Oral Cancer

Our recent study established the increased circulating microparticles (MPs) and their procoagulant activity in oral squamous cell carcinoma (OSCC). In the present study, we further evaluated different phenotypes of circulating MPs in OSCC patients and explored their clinical significance and effects on angiogenesis (a critical event in tumor progression). To conduct the study, circulating MPs in 45 OSCC patients and 18 healthy volunteers were characterized and quantified by transmission electron microscopy and flow cytometry. Correlations between circulating MPs and clinicopathologic data, microvessel density, and proangiogenic factor levels in patients with OSCC were analyzed by immunohistochemistry and Spearman rank correlation test. Additionally, the in vitro studies were performed with use of human umbilical vein endothelial cells. Our results showed that the levels of circulating MPs as well as the subsets of platelet-derived, endothelium-derived, and pan-leukocyte MPs in stages III to IV OSCC were significantly higher than stages I to II and healthy subjects. Moreover, these increased circulating MPs were significantly correlated with tumor size, TNM stages, microvessel density, and expression levels of vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP9) in OSCC patients. The in vitro studies revealed that circulating MPs isolated from OSCC patients could be effectively taken up by human umbilical vein endothelial cells and could promote the proliferation, migration, invasion, and tube formation of recipient endothelial cells, accompanied by increased expression of proangiogenic factors. In summary, circulating MPs play important roles in angiogenesis and local tumor progression of OSCC. Our results shed new light on the progression of OSCC and might be helpful to explore novel treatment strategies targeting tumor angiogenesis.