SNAI1-expressing fibroblasts and derived-extracellular matrix as mediators of drug resistance in colorectal cancer patients.

Autor: Galindo-Pumariño C; Medical Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain., Collado M; Medical Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain., Castillo ME; Medical Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain; Universidad Alfonso X El Sabio, 28691 Madrid, Spain., Barquín J; Surgical Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain., Romio E; Pathology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain., Larriba MJ; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: mjlarriba@iib.uam.es., Muñoz de Mier GJ; Universidad Alfonso X El Sabio, 28691 Madrid, Spain. Electronic address: gmunodem@uax.es., Carrato A; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain., de la Pinta C; Radiation Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain. Electronic address: cdelapinta88@gmail.com., Pena C; Medical Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Universidad Alfonso X El Sabio, 28691 Madrid, Spain. Electronic address: cristinapenamaroto@gmail.com.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2022 Sep 01; Vol. 450, pp. 116171. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1016/j.taap.2022.116171
Abstrakt: Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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