Microvesicles derived from squamous cell carcinoma induce cell death, autophagy, and invasion of benign myoepithelial cells.

Autor: Martinez EF; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., de Araújo VC; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., Navarini NF; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., de Souza IF; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., Rena GB; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., Demasi APD; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil., de Paula E; Department of Biochemistry and Tissue Biology, Biology Institute, State University of Campinas, Campinas, SP, Brazil., Teixeira LN; Cell Biology and Oral Pathology Division, Faculdade São Leopoldo Mandic, Campinas, SP, Brazil.
Jazyk: angličtina
Zdroj: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology [J Oral Pathol Med] 2020 Sep; Vol. 49 (8), pp. 761-770. Date of Electronic Publication: 2020 Jun 11.
DOI: 10.1111/jop.13037
Abstrakt: 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 proliferation via growth 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 × 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 modulate BAX, SURVIVIN, LC3B, MMP-2, and MMP-9 expression. 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.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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