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Open AccessReview

TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer

1
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Box 582, 75123 Uppsala, Sweden
2
National Institute of Gastroenterology, “S. de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy
3
TGF-β and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l’Hospitalet, 199, 08908 Barcelona, Spain
4
Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain
5
Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, L’Hospitalet, 08907 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1294; https://doi.org/10.3390/ijms19051294
Received: 27 March 2018 / Revised: 17 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
(This article belongs to the Special Issue TGF-beta Family in Fibrosis and Cancer)
Transforming growth factor-β (TGF-β) is a cytokine essential for the induction of the fibrotic response and for the activation of the cancer stroma. Strong evidence suggests that a strong cross-talk exists among TGF-β and the tissue extracellular matrix components. TGF-β is stored in the matrix as part of a large latent complex bound to the latent TGF-β binding protein (LTBP) and matrix binding of latent TGF-β complexes, which is required for an adequate TGF-β function. Once TGF-β is activated, it regulates extracellular matrix remodelling and promotes a fibroblast to myofibroblast transition, which is essential in fibrotic processes. This cytokine also acts on other cell types present in the fibrotic and tumour microenvironment, such as epithelial, endothelial cells or macrophages and it contributes to the cancer-associated fibroblast (CAF) phenotype. Furthermore, TGF-β exerts anti-tumour activity by inhibiting the host tumour immunosurveillance. Aim of this review is to update how TGF-β and the tissue microenvironment cooperate to promote the pleiotropic actions that regulate cell responses of different cell types, essential for the development of fibrosis and tumour progression. We discuss recent evidences suggesting the use of TGF-β chemical inhibitors as a new line of defence against fibrotic disorders or cancer. View Full-Text
Keywords: TGF-β; fibrosis; cancer; HCC; microenvironment; CAF; hepatic stellate cells; extracellular matrix; galunisertib TGF-β; fibrosis; cancer; HCC; microenvironment; CAF; hepatic stellate cells; extracellular matrix; galunisertib
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MDPI and ACS Style

Caja, L.; Dituri, F.; Mancarella, S.; Caballero-Diaz, D.; Moustakas, A.; Giannelli, G.; Fabregat, I. TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer. Int. J. Mol. Sci. 2018, 19, 1294. https://doi.org/10.3390/ijms19051294

AMA Style

Caja L, Dituri F, Mancarella S, Caballero-Diaz D, Moustakas A, Giannelli G, Fabregat I. TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer. International Journal of Molecular Sciences. 2018; 19(5):1294. https://doi.org/10.3390/ijms19051294

Chicago/Turabian Style

Caja, Laia; Dituri, Francesco; Mancarella, Serena; Caballero-Diaz, Daniel; Moustakas, Aristidis; Giannelli, Gianluigi; Fabregat, Isabel. 2018. "TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer" Int. J. Mol. Sci. 19, no. 5: 1294. https://doi.org/10.3390/ijms19051294

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