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

Abstract

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.

Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

“…Circulating tumor cells (e.g., of gastric, ovarian, oral, and prostate cancer) may activate platelets resulting in a production of small microparticles (MPs) that contain membrane receptors as well as cytoplasmic constituents [ 55 – 57 ]. Platelet-derived microparticles (PMPs) play a role in tumor growth and invasiveness (at least in part by stimulation of MMP-2 production), and angiogenesis [by releasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)], as well as induce metastasis [ 58 ].…”

Characterization of microparticles in patients with venous malformations of the head and neck

“…The obtained MP were quantified by flow cytometry using BD FACSAria III flow cytometer (BD Biosciences, USA) as similar to our previous reports (Chen et al , ; Ren et al , ,b). Briefly, when a sample is loaded into FACSAria, the count of ‘events’ could be detected and obtained through flow cytometer.…”

“…MP were isolated from peripheral venous blood (circulating MP) or lesional fluid from VM patients (lesional MP) as similar to our previous studies (Ren et al , ,b). Briefly, venous blood (5 ml) was collected on citrated tubes from VM patients or healthy volunteers while lesional fluid was drawn from VM patients.…”

Exosomes and other extracellular vesicles in oral and salivary gland cancers

“…Over the past decade, a considerable proportion of studies have strongly supported that EVs can accelerate tumor angiogenesis and thus promote the growth of oral cancer (de Andrade et al, ; Dickman et al, ; Ren, Zhang, et al, ). The transmembrane receptors in the TGF‐β pathway, TGF‐β receptor I (TβRI) and TGF‐β receptor II (TβRII), have been shown to be involved in EV‐mediated angiogenesis in oral cancer.…”

“…Circulating microparticles (MPs) are small phospholipid vesicles (0.1–1 μm diameter) derived from vascular endothelium or circulating blood cells in the peripheral blood (Piccin, Murphy, & Smith, ). MPs can promote angiogenesis in OSCC by activating coagulation (Ren, Zhang, et al, ), and an elevated level of platelet‐derived MPs may contribute to an increased procoagulant activity in patients with OSCC and possibly be associated with a poor prognosis (Ren, Man, et al, ).…”