000110880 001__ 110880
000110880 005__ 20230519145618.0
000110880 0247_ $$2doi$$a10.3390/cancers13225613
000110880 0248_ $$2sideral$$a127548
000110880 037__ $$aART-2021-127548
000110880 041__ $$aeng
000110880 100__ $$aGallego Rentero M.
000110880 245__ $$aTgfß1 secreted by cancer-associated fibroblasts as an inductor of resistance to photodynamic therapy in squamous cell carcinoma cells
000110880 260__ $$c2021
000110880 5060_ $$aAccess copy available to the general public$$fUnrestricted
000110880 5203_ $$aAs an important component of tumor microenvironment, cancer-associated fibroblasts (CAFs) have lately gained prominence owing to their crucial role in the resistance to therapies. Photodynamic therapy (PDT) stands out as a successful therapeutic strategy to treat cutaneous squamous cell carcinoma. In this study, we demonstrate that the transforming growth factor ß1 (TGFß1) cytokine secreted by CAFs isolated from patients with SCC can drive resistance to PDT in epithelial SCC cells. To this end, CAFs obtained from patients with in situ cSCC were firstly characterized based on the expression levels of paramount markers as well as the levels of TGFß1 secreted to the extracellular environment. On a step forward, two established human cSCC cell lines (A431 and SCC13) were pre-treated with conditioned medium obtained from the selected CAF cultures. The CAF-derived conditioned medium effectively induced resistance to PDT in A431 cells through a reduction in the cell proliferation rate. This resistance effect was recapitulated by treating with recombinant TGFß1 and abolished by using the SB525334 TGFß1 receptor inhibitor, providing robust evidence of the role of TGFß1 secreted by CAFs in the development of resistance to PDT in this cell line. Conversely, higher levels of recombinant TGFß1 were needed to reduce cell proliferation in SCC13 cells, and no induction of resistance to PDT was observed in this cell line in response to CAF-derived conditioned medium. Interestingly, we probed that the comparatively higher intrinsic resistance to PDT of SCC13 cells was mediated by the elevated levels of TGFß1 secreted by this cell line. Our results point at this feature as a promising biomarker to predict both the suitability of PDT and the chances to optimize the treatment by targeting CAF-derived TGFß1 in the road to a more personalized treatment of particular cSCC tumors. © 2021 by the authors.
000110880 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII-FEDER/FIS PI18-00708$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII-FEDER/FIS PI18-00858
000110880 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000110880 590__ $$a6.575$$b2021
000110880 592__ $$a1.349$$b2021
000110880 594__ $$a5.8$$b2021
000110880 591__ $$aONCOLOGY$$b60 / 245 = 0.245$$c2021$$dQ1$$eT1
000110880 593__ $$aOncology$$c2021$$dQ1
000110880 593__ $$aCancer Research$$c2021$$dQ1
000110880 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000110880 700__ $$aGutiérrez Pérez M.
000110880 700__ $$aFernández Guarino M.
000110880 700__ $$0(orcid)0000-0001-8034-3617$$aMascaraque, M.$$uUniversidad de Zaragoza
000110880 700__ $$aPortillo Esnaola M.
000110880 700__ $$aGilaberte, Y.
000110880 700__ $$aCarrasco, E.
000110880 700__ $$aJuarranz, Á.
000110880 7102_ $$11007$$2183$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cÁrea Dermatología
000110880 773__ $$g13, 22 (2021), 5613 [24 pp.]$$pCancers$$tCancers$$x2072-6694
000110880 8564_ $$s3932599$$uhttps://zaguan.unizar.es/record/110880/files/texto_completo.pdf$$yVersión publicada
000110880 8564_ $$s2811838$$uhttps://zaguan.unizar.es/record/110880/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000110880 909CO $$ooai:zaguan.unizar.es:110880$$particulos$$pdriver
000110880 951__ $$a2023-05-18-16:13:00
000110880 980__ $$aARTICLE