garp-tgf-beta1

Overview

GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking protein for latent transforming growth factor-β1 (TGF-β1) that is expressed on activated regulatory T lymphocytes, activated B cells, and platelets. GARP regulates the localization and activation of TGF-β1.1


  • TGF-β1 is a pleiotropic cytokine that plays important roles in numerous aspects of biological processes such as cell proliferation, development, apoptosis, fibrosis, angiogenesis, wound healing, and cancer, in addition to other processes.1
  • GARP has been identified as a critical regulator of TGF-β1 expression and activation. By binding to latent TGF-β1, GARP acts as a docking receptor that concentrates latent TGF-β on the cell surface and enhances its final activation.1
  • On the cell surface, GARP-latent TGF-β1 complex associates with integrins (αVβ6 and αVβ8) to release active TGF-β1 . Mature TGF-β1 interacts with TGF-β receptors on the cell surface.
(Adapted from Metelli A, et al. Journal of Hematology & Oncology (2018) 11:24. http://creativecommons.org/licenses/by/4.0/ for CC BY 4.0 )

IMPLICATIONS IN CANCER

In a xenograft model, GARP overexpression promoted Foxp3+ Treg activity, which in turn contributed to enhancing cancer progression and metastasis.2

Oncogenic Expression1

  • GARP supports TGF-β1-driven cancer cell growth and dissemination by regulating the innate and adaptive immune system and favors tumor immune evasion.
  • Active TGF-β1 impairs adaptive anti-tumor immunity by directly inhibiting the clonal expansion and cytotoxicity of the CD8+ cytotoxic T cells (CTLs).
  1. Metelli A, et al. Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer. Journal of Hematology & Oncology. (2018) 11:24.
  2. Metelli A, et al. Surface Expression of TGFb Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer. Cancer Res. 2016; 76(24) 7106-7117.

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