TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells

As 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. I...

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Autores principales:	María Gallego-Rentero, María Gutiérrez-Pérez, Montserrat Fernández-Guarino, Marta Mascaraque, Mikel Portillo-Esnaola, Yolanda Gilaberte, Elisa Carrasco, Ángeles Juarranz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancer-associated fibroblasts photodynamic therapy squamous cell carcinoma TGFβ resistance tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ac1da7e5369448aaba07489d5596db2d
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spelling	oai:doaj.org-article:ac1da7e5369448aaba07489d5596db2d2021-11-25T17:01:35ZTGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells10.3390/cancers132256132072-6694https://doaj.org/article/ac1da7e5369448aaba07489d5596db2d2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5613https://doaj.org/toc/2072-6694As 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 β1 (TGFβ1) 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 TGFβ1 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 TGFβ1 and abolished by using the SB525334 TGFβ1 receptor inhibitor, providing robust evidence of the role of TGFβ1 secreted by CAFs in the development of resistance to PDT in this cell line. Conversely, higher levels of recombinant TGFβ1 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 TGFβ1 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 TGFβ1 in the road to a more personalized treatment of particular cSCC tumors.María Gallego-RenteroMaría Gutiérrez-PérezMontserrat Fernández-GuarinoMarta MascaraqueMikel Portillo-EsnaolaYolanda GilaberteElisa CarrascoÁngeles JuarranzMDPI AGarticlecancer-associated fibroblastsphotodynamic therapysquamous cell carcinomaTGFβresistancetumor microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5613, p 5613 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer-associated fibroblasts photodynamic therapy squamous cell carcinoma TGFβ resistance tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cancer-associated fibroblasts photodynamic therapy squamous cell carcinoma TGFβ resistance tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 María Gallego-Rentero María Gutiérrez-Pérez Montserrat Fernández-Guarino Marta Mascaraque Mikel Portillo-Esnaola Yolanda Gilaberte Elisa Carrasco Ángeles Juarranz TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
description	As 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 β1 (TGFβ1) 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 TGFβ1 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 TGFβ1 and abolished by using the SB525334 TGFβ1 receptor inhibitor, providing robust evidence of the role of TGFβ1 secreted by CAFs in the development of resistance to PDT in this cell line. Conversely, higher levels of recombinant TGFβ1 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 TGFβ1 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 TGFβ1 in the road to a more personalized treatment of particular cSCC tumors.
format	article
author	María Gallego-Rentero María Gutiérrez-Pérez Montserrat Fernández-Guarino Marta Mascaraque Mikel Portillo-Esnaola Yolanda Gilaberte Elisa Carrasco Ángeles Juarranz
author_facet	María Gallego-Rentero María Gutiérrez-Pérez Montserrat Fernández-Guarino Marta Mascaraque Mikel Portillo-Esnaola Yolanda Gilaberte Elisa Carrasco Ángeles Juarranz
author_sort	María Gallego-Rentero
title	TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
title_short	TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
title_full	TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
title_fullStr	TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
title_full_unstemmed	TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells
title_sort	tgfβ1 secreted by cancer-associated fibroblasts as an inductor of resistance to photodynamic therapy in squamous cell carcinoma cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ac1da7e5369448aaba07489d5596db2d
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TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells

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