Salivary non-apoptotic tumoral microvesicles: A potential progressive marker in oral cancer patients.

Abstract

Tumour cell-secreted microvesicles (MVs) contribute immensely to tumour progression. However, the role of tumoral salivary MVs in oral squamous cell carcinoma (OSCC) remains unclear. Herein, we elucidated the role of non-apoptotic salivary tumoral MVs in OSCC development, especially relating to the migration ability. We purified and compared non-apoptotic salivary tumoral MVs from 63 OSCC patients and orthotopic OSCC mice model. Next, we compared the protein difference between apoptotic and non-apoptotic MVs by Western blot, proteomics and flow cytometry from saliva and CAL27 cells. Finally, we collected the non-apoptotic MVs and co-cultured with normal oral epithelial cells, the migration ability was examined by wound healing assay and Western blot assay. Our results indicated that the levels of non-apoptotic tumoral S-MVs were significantly higher in OSCC patients with T3 to T4 stages than in patients with T1 to T2 stages or healthy donors. In OSCC mice model, we found elevations of non-apoptotic tumoral MVs associated with tumoral volume. EGFR overexpression increased the generation of non-apoptotic tumoral MVs which could significantly promote normal epithelial cell migration. In conclusion, elevated levels of non-apoptotic tumoral S-MVs are associated with clinicopathologic features of OSCC patients, implying that non-apoptotic tumoral S-MVs are a potential progressive marker of OSCC.