Title: Microvesicles derived from squamous cell carcinoma induce cell death, autophagy and invasion of benign myoepithelial cells
Author: Martinez, Elizabeth Ferreira; De Araújo, Vera Cavalcanti; Navarini, Natalia Festugatto; De Souza, Isabela Fernandes; Rena, Gabriel Bernardo; Demasi, Ana Paula Dias; De Paula, Eneida; Teixeira, Lucas Novaes
Is part of: JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 49, p. 761 - 770
Citation: Martinez, Elizabeth Ferreira; De Araújo, Vera Cavalcanti; Navarini, Natalia Festugatto; De Souza, Isabela Fernandes; Rena, Gabriel Bernardo; Demasi, Ana Paula Dias; De Paula, Eneida; Teixeira, Lucas Novaes; Microvesicles derived from squamous cell carcinoma induce cell death, autophagy and invasion of benign myoepithelial cells. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v.49, p. 761-770, 2020
Abstract: Background There has been great interest recently in the mechanisms of cell-to-cell communication through microvesicles (MV). These structures are produced by many different cell types and can modulate cellular activity by induction of epigenetic alterations. These vesicles may promote tumor mass increase either by stimulating cell proliferationviagrowth factors or by inhibiting apoptosis, which reinforces the role of such vesicles as important modulators of tumor progression. Methods The present in vitro study aimed to characterize MV derived from malignant neoplastic epithelial cell cultures (EP) and their effect on the expression of apoptosis/autophagy and invasion related genes of benign myoepithelial (Myo) cell cultures. Results The results revealed round structures with a mean size of 153.6 (+/- 0.2) nm, with typical MV morphology. CD63 quantification indicated that EP cell culture at 70%-80% confluence secreted 3.088 x 10(8)MV/mL. Overall, Myo exposed to MVs derived from EP showed both up- and downregulation of tumorigenesis promoting genes. MVs from EP cells promoted cell death of Myo cells and positively modulateBAX,SURVIVIN,LC3B, MMP-2,andMMP-9expression. Furthermore, an increasing of MMP-2 and MMP-9 secretion by Myo was observed after MV exposure. Conclusions These findings suggest that MVs from EP modulate autophagy of Myo cells, which may, in part, explain the disappearance of these cells in in situ areas of invasive carcinoma ex-pleomorphic adenoma. Additionally, the overexpression of MMPs contributes to the development of an invasive phenotype of Myo cells, which could favor the dissolution of the basement membrane during tumorigenesis process.
Keywords: exosomes; nanotracking analysis;
Subjects: CIENCIAS_BIOLOGICAS; Farmacologia Bioquímica e Molecular;
Funding: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Grant/Award Number: 2015/16289-5 and 2017/04704-3; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Grant/Award Number: 302138/2017-0; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Grant/Award Number: 20132146