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Aspirin Affects MDA-MB-231 Vesicle Production and Their Capacity to Induce Fibroblasts towards a Pro-Invasive State.
Louback, Rafaela de Assiz; Martins-Cardoso, Karina; Tinoco, Luzineide W; Collino, Federica; de Barros, Ana Paula D N; Fortuna-Costa, Anneliese; Monteiro, Robson Q; Rossi, Maria Isabel Doria; Lindoso, Rafael Soares.
Afiliação
  • Louback RA; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
  • Martins-Cardoso K; Clementino Fraga Filho University Hospiyal, Federal University of Rio de Janeiro, Rio de Janeiro 21941913, Brazil.
  • Tinoco LW; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
  • Collino F; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
  • de Barros APDN; Laboratory for Analysis and Development of Enzyme Inhibitors, Natural Products Research Institute, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
  • Fortuna-Costa A; Department of Clinical Sciences and Community Health, University of Milano, 20122 Milan, Italy.
  • Monteiro RQ; Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Rossi MID; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Lindoso RS; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
Int J Mol Sci ; 24(15)2023 Jul 27.
Article em En | MEDLINE | ID: mdl-37569393
Long-term administration of aspirin (ASA, acetylsalicylic acid) in oncogenic patients has been related to a reduction in cancer risk incidence, but its precise mechanism of action is unclear. The activation of cancer-associated fibroblasts (CAFs) is a key element in tumor progression and can be triggered by cancer-derived extracellular vesicles (EVs). Targeting the communication between cancer cells and the surrounding tumor microenvironment (TME) may control cancer progression. Our aim was to investigate the effect of ASA on breast cancer cells, focusing on EV secretion and their effect on the biological properties of CAFs. As a result, ASA was shown to reduce the amount and alter the size distribution of EVs produced by MDA-MB-231 tumor cells. Fibroblasts stimulated with EVs derived from MDA-MB-231 treated with ASA (EV-ASA) showed a lower expression of alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP2) but not fibroblast activation protein (FAP) in respect to the ones stimulated with EVs from untreated breast cancer cells (EV-CTR). Furthermore, invasion assays using a three-dimensional (3D) fibroblast spheroid model showed reduced MDA-MB-231 invasion towards fibroblast spheroids pretreated with EV-ASA as compared to spheroids prepared with EV-CTR-stimulated fibroblasts. This suggests that ASA partially inhibits the ability of tumor EVs to stimulate CAFs to promote cancer invasion. In conclusion, ASA can interfere with tumor communication by reducing EV secretion by breast tumor cells as well as by interfering with their capacity to stimulate fibroblasts to become CAFs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça