Matrix metalloproteinase and G protein coupled receptors: co-conspirators in the pathogenesis of autoimmune disease and cancer

J Autoimmun. Nov-Dec 2009;33(3-4):214-21. doi: 10.1016/j.jaut.2009.09.011. Epub 2009 Oct 1.

Abstract

Similarities in the pathologies of autoimmune diseases and cancer have been noted for at least 30 years. Inflammatory cytokines and growth factors mediate cell proliferation, and proteinases, especially the collagenase, Matrix Metalloproteinase-1 (MMP-1), contribute to disease progression by remodeling the extracellular matrix and modulating the microenvironment. This review focuses on two cancers (melanoma and breast) and on the autoimmune disorder, rheumatoid arthritis (RA), and discusses the activated stromal cells found in these diseases. MMP-1 was originally thought to function only to degrade interstitial collagens, but recent studies have revealed novel roles for MMP-1 involving the G protein-coupled receptors: the chemokine receptor, CXCR-4, and Protease Activated Receptor-1 (PAR-1). Cooperativity between MMP-1 and CXCR4/SDF-1 signaling influences the behavior of activated fibroblasts in both RA and cancer. Further, MMP-1 is a vital part of an autocrine/paracrine MMP-1/PAR-1 signal transduction axis, a function that amplifies its potential to remodel the matrix and to modify cell behavior. Finally, new therapeutic agents directed at MMP-1 and G protein-coupled receptors are emerging. Even though these agents are more specific in their targets than past therapies, these targets are often shared between RA and cancer, underscoring fundamental similarities between autoimmune disorders and some cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Endothelial Cells / immunology
  • Female
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Humans
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Skin Neoplasms / immunology*
  • Stromal Cells / immunology

Substances

  • Anticarcinogenic Agents
  • Antirheumatic Agents
  • Receptors, G-Protein-Coupled
  • Matrix Metalloproteinases