Tissue factor mediates microvesicles shedding from MDA-MB-231 breast cancer cells.

Autor: Rondon AMR; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Brazil; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, The Netherlands., de Almeida VH; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Brazil., Gomes T; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Brazil., Verçoza BRF; Núcleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-BIO), Polo Avançado de Xerém, UFRJ, Duque de Caxias, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, RJ, Brazil., Carvalho RS; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, UFRJ, Brazil., König S; Institute of Biomedical Sciences, UFRJ, Brazil., Rodrigues JCF; Núcleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-BIO), Polo Avançado de Xerém, UFRJ, Duque de Caxias, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, RJ, Brazil., Mermelstein CDS; Institute of Biomedical Sciences, UFRJ, Brazil., Versteeg HH; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, The Netherlands., Monteiro RQ; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Brazil. Electronic address: robsonqm@bioqmed.ufrj.br.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Jul 07; Vol. 502 (1), pp. 137-144. Date of Electronic Publication: 2018 May 24.
DOI: 10.1016/j.bbrc.2018.05.136
Abstrakt: Extracellular vesicles, such as microvesicles (MVs), were identified as important players in tumor progression and acquisition of an aggressive phenotype. Tissue factor (TF) is a transmembrane protein that initiates the blood coagulation cascade. In tumor cells, TF has been associated with aggressiveness and cancer progression. Previous studies demonstrate that TF is incorporated into MVs secreted by tumor cells; however, it is unknown whether TF is actively involved in the release of MVs. Here, we investigated the influence of TF expression on the release of MVs. TF silencing was achieved through CRISPR/Cas9 approaches in the human breast cancer cell line, MDA-MB-231. TF knockout in MDA-MB-231 cells efficiently reduced TF-dependent signaling and procoagulant activity. Remarkably, silencing of TF caused a significant decrease in the number of MVs released by MDA-MB-231 cells. We also observed an increase in actin-positive membrane projections in TF knockout cells and a reduction in RhoA expression when compared to TF-expressing cells. Treatment of MDA-MB-231 cells with the RhoA-ROCK signaling pathway inhibitor, fasudil, significantly reduced the release of MVs. Taken together, our results suggest a novel and relevant role for TF in tumor biology by playing an active role in the MVs secretion.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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