Abstract A34: Effect of microvesicles on metalloproteinases secretion by myoepithelial cells

Abstract

Abstract In tumorigenesis, not only genetic and epigenetic alterations but also stromal cells and soluble factors in the tumor microenvironment can affect the progression of different neoplasms. In salivary gland tumors derived from the intercalated duct, the myoepithelial (Myo) component modulates the neoplastic phenotype positively. Indeed, in carcinoma ex-pleomorphic adenoma (CXPA) where the malignant component is represented only by epithelial cells, the Myo cells present a role in the progression of this neoplasia. Nevertheless, great interest has been taken in the mechanisms of cellular communication mediated by microvesicles (MV). These structures are secreted by different cells and may induce epigenetic modifications. In malignant neoplasia, MV may affect different stages of carcinogenesis, which comprise the modulation of the extracellular matrix components, including metalloproteinases (MMPs). MMPs 2 and 9 exert an essential role in the epithelial-mesenchymal transition, consequently increasing the potential of migration and invasion of plethora tumors, including CXPA. The present in vitro study aimed to characterize MV derived from malignant neoplastic epithelial cell cultures (CAL27 cells) and their effect on the expression of MMPs in benign Myo cell cultures. Malignant epithelial cells (CAL 27 cell line) were cultured until they reached confluence. Then, the culture medium was collected and the MV were extracted. The Myo cultures, derived from pleomorphic adenomas explants, were exposed to MV from CAL 27 for 24 h. After this period, the secretion of MMPs 2, 9 and their inhibitors, TIMP-1 and TIMP-2, was assayed by means of ELISA. The Myo cultures not exposed to MV were used as control. The results indicated that Myo exposed to MV exhibited a significant increase of MMP-2 and MMP-9 expression (p<0.05) and a reduction in TIMP-2 expression (p<0.05). TIMP-1 expression in Myo cultures was not affected by MV (p>0.05). In conclusion, the data suggest that MV can modulate MMP and their inhibitors’ expression in Myo cell, which may promote extracellular matrix degradation and CXPA invasion. Citation Format: Gabriel Bernardo Rena, Lucas Novaes Teixeira, Vera Cavalcanti Araújo, Ana Paula Dias Demasi, Elizabeth Ferreira Martinez. Effect of microvesicles on metalloproteinases secretion by myoepithelial cells [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A34.