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DNA methylation profiling unveils TGF-ß hyperresponse in tumor associated fibroblasts from lung cancer patients
Vizioso, Miguel; Puig, Marta; Carmona, F. Javier; Maqueda González, María de los Ángeles; Gomez, Antonio; Labernardie, nna; Gabasa, Marta; Mendizuri, Saloa; Ikemori, Rafael; Trepat Guixer, Xavier; Moran, Sebastian; Vidal, Enrique; Reguart, Noemí; Perera Lluna, Alexandre; Esteller, Manel; Alcaraz, Jordi
Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial; Universitat Politècnica de Catalunya. SISBIO - Senyals i Sistemes Biomèdics
There is growing interest in defining the aberrant molecular differences between normal and tumor-associated fibroblasts (TAFs) that support tumor progression. For this purpose, we recently conducted a genome-wide DNA methylation profiling of TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer (NSCLC) patients, and reported a widespread hypomethylation concomitantly with focal gain of DNA methylation; in addition, we found evidence that a fraction of lung TAFs are fibrocytes in origin. Of note, the aberrant epigenome of lung TAFs had a global impact in gene expression and a selective impact on the TGF-ß pathway. To get insights on the functional implications of the latter impact, we analyzed the response of lung TAFs to exogenous TGF-ß1 in terms of activation and contractility. We found a larger expression of a panel of activation markers including a-SMA and collagen-I in TAFs compared to control fibroblasts. Likewise, TGF-ß1 elicited a larger contractility in TAFs than in CFs as assessed by traction force microscopy. These findings reveal that lung TAFs are hyperresponsive to TGF-ß1, which may underlie the expansion and/or maintenance of the tumor-promoting desmoplastic stroma in lung cancer.
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
Bioinformatics
Bioinformàtica
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/submittedVersion
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