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

Laia Caja, Francesco Dituri, Serena Mancarella, Daniel Caballero-Diaz, Aristidis Moustakas, Gianluigi Giannelli, Isabel Fabregat

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)1294
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
Publication statusPublished - Apr 26 2018

Fingerprint

fibrosis
Tumors
Fibrosis
tumors
cancer
Tissue
fibroblasts
Fibroblasts
matrices
Neoplasms
cells
Extracellular Matrix
Cytokines
phenotype
macrophages
Macrophages
Endothelial cells
Transforming Growth Factors
Immunologic Monitoring
progressions

Keywords

  • Animals
  • Carcinoma, Hepatocellular/metabolism
  • Cellular Microenvironment
  • Extracellular Matrix/metabolism
  • Humans
  • Liver Cirrhosis/metabolism
  • Liver Neoplasms/metabolism
  • Transforming Growth Factor beta/genetics

Cite this

TGF-β and the Tissue Microenvironment : Relevance in Fibrosis and Cancer. / Caja, Laia; Dituri, Francesco; Mancarella, Serena; Caballero-Diaz, Daniel; Moustakas, Aristidis; Giannelli, Gianluigi; Fabregat, Isabel.

In: International Journal of Molecular Sciences, Vol. 19, No. 5, 26.04.2018, p. 1294.

Research output: Contribution to journalReview article

Caja, Laia ; Dituri, Francesco ; Mancarella, Serena ; Caballero-Diaz, Daniel ; Moustakas, Aristidis ; Giannelli, Gianluigi ; Fabregat, Isabel. / TGF-β and the Tissue Microenvironment : Relevance in Fibrosis and Cancer. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 5. pp. 1294.
@article{d40b873197384299a2f975c72b637cb8,
title = "TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer",
abstract = "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.",
keywords = "Animals, Carcinoma, Hepatocellular/metabolism, Cellular Microenvironment, Extracellular Matrix/metabolism, Humans, Liver Cirrhosis/metabolism, Liver Neoplasms/metabolism, Transforming Growth Factor beta/genetics",
author = "Laia Caja and Francesco Dituri and Serena Mancarella and Daniel Caballero-Diaz and Aristidis Moustakas and Gianluigi Giannelli and Isabel Fabregat",
year = "2018",
month = "4",
day = "26",
doi = "10.3390/ijms19051294",
language = "English",
volume = "19",
pages = "1294",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "5",

}

TY - JOUR

T1 - TGF-β and the Tissue Microenvironment

T2 - Relevance in Fibrosis and Cancer

AU - Caja, Laia

AU - Dituri, Francesco

AU - Mancarella, Serena

AU - Caballero-Diaz, Daniel

AU - Moustakas, Aristidis

AU - Giannelli, Gianluigi

AU - Fabregat, Isabel

PY - 2018/4/26

Y1 - 2018/4/26

N2 - 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.

AB - 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.

KW - Animals

KW - Carcinoma, Hepatocellular/metabolism

KW - Cellular Microenvironment

KW - Extracellular Matrix/metabolism

KW - Humans

KW - Liver Cirrhosis/metabolism

KW - Liver Neoplasms/metabolism

KW - Transforming Growth Factor beta/genetics

U2 - 10.3390/ijms19051294

DO - 10.3390/ijms19051294

M3 - Review article

C2 - 29701666

VL - 19

SP - 1294

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 5

ER -