Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer

Digestion. 2020;101(1):18-24. doi: 10.1159/000504087. Epub 2019 Nov 13.


Background: Cancer tissues consist of cancer cells and stroma, the latter of which dictates cancer tissue microenvironment. We recently reported that the desmoplastic reaction (DR) pattern at the invasive front in colorectal cancer (CRC) is a promising prognostic indicator. However, the molecular mechanisms of DR formation and contribution to patients' prognosis remain unclear.

Summary: The tumor tissue microenvironment composed of extracellular matrix (ECM), soluble factors (growth factors/cytokine/cytokine), and stromal cells controls tumor growth and spread. Among stromal cells, cancer-associated fibroblasts (CAFs) play a key role in development of the cancer tissue microenvironment, and they are responsible for DR formation. CAFs express a disintegrin and metalloproteinases (ADAMs), which modulate cancer tissue microenvironmental factors. We isolated CAFs and normal fibroblasts from colon tissues of patients with CRC and characterized them. CAFs showed the increased expression of several ADAM species including ADAM9, ADAM10, ADAM12, and ADAM17, and the expression was further increased on the ECM-coated plates. Our in vitro and in vivo studies using CAFs and CRC cells suggest that ADAM expression is associated with the morphological DR category, and ADAMs may affect cancer malignancy through tumor proliferation in CRC. Key Message: This review summarizes the present knowledge on ADAMs in cancer and describes our recent findings regarding the molecular biological background of DR mainly by focusing on ADAMs.

Keywords: A disintegrin and metalloproteinase; Cancer-associated fibroblast; Colorectal cancer; Desmoplastic reaction.

Publication types

  • Review

MeSH terms

  • ADAM Proteins / biosynthesis
  • ADAM Proteins / metabolism*
  • Animals
  • Biomarkers, Tumor / metabolism
  • Cancer-Associated Fibroblasts / metabolism*
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Disease Progression
  • Extracellular Matrix / metabolism
  • Fibroblasts / metabolism*
  • Fibrosis / metabolism
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Prognosis
  • Stromal Cells / metabolism
  • Tumor Cells, Cultured
  • Tumor Microenvironment


  • Biomarkers, Tumor
  • ADAM Proteins