Cancer-Associated Fibroblasts in Mycosis Fungoides Promote Tumor Cell Migration and Drug Resistance through CXCL12/CXCR4
نویسندگان
چکیده
Cancer cells are known to reprogram normal fibroblasts into cancer-associated (CAFs) act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type cutaneous T-cell lymphoma, unknown. This study sought characterize MF their cross talk with lymphoma using primary fibroblast cultures from punch biopsies patients early-stage healthy subjects. yielded significantly increased levels FAP?, a CAF marker, CAF-associated genes proteins: CXCL12 (ligand CXCR4 expressed on cells), collagen XI, matrix metalloproteinase 2. Cultured showed greater proliferation than ex vivo experiments. A coculture MyLa (MF cell line) growth, reduced sensitivity doxorubicin, enhanced migration. Inhibiting CXCL12/CXCR4 axis doxorubicin-induced apoptosis motility. Our data suggest that lesions more proliferative skin protect death increase migration through secretion CXCL12. Reversing CAF-mediated microenvironment may improve efficiency anticancer therapy. 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Indeed, tended migrate Inhibition motility migrating finding indicates acts chemoattractant CXCR4-expressing antagonist present. well-known suppresses NF-?B activation, Bcl-2 directly pro-apoptotic BAD (Bcl-xl/Bcl-2?associated promoter), indirect transcription factor cAMP component?binding (Ganju 1998Ganju R.K. Brubaker S.A. Meyer Dutt Qin ?-chemokine, factor-1?, transmembrane G-protein-coupled CXCR-4 receptor transduction pathways.J Biol Chem. 1998; 273: 23169-23175Abstract (AMD3100) prevents antiapoptotic induced but protected Doxo. protection attenuated adding antagonist. supports CAF-derived mediating chemotherapy. numerous support use antagonists disrupt CXCR4-dependent tumor?stroma interactions thus sensitize chemotherapy (Burger Peled, 2009Burger J.A. 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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2021
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2020.06.034