The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer

Front Immunol. 2023 Jan 19:13:1093990. doi: 10.3389/fimmu.2022.1093990. eCollection 2022.

Abstract

Matrix metalloproteinases (MMPs) are an important class of enzymes in the body that function through the extracellular matrix (ECM). They are involved in diverse pathophysiological processes, such as tumor invasion and metastasis, cardiovascular diseases, arthritis, periodontal disease, osteogenesis imperfecta, and diseases of the central nervous system. MMPs participate in the occurrence and development of numerous cancers and are closely related to immunity. In the present study, we review the immunomodulatory role of MMPs in colitis-associated cancer (CAC) and discuss relevant clinical applications. We analyze more than 300 pharmacological studies retrieved from PubMed and the Web of Science, related to MMPs, cancer, colitis, CAC, and immunomodulation. Key MMPs that interfere with pathological processes in CAC such as MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13, as well as their corresponding mechanisms are elaborated. MMPs are involved in cell proliferation, cell differentiation, angiogenesis, ECM remodeling, and the inflammatory response in CAC. They also affect the immune system by modulating differentiation and immune activity of immune cells, recruitment of macrophages, and recruitment of neutrophils. Herein we describe the immunomodulatory role of MMPs in CAC to facilitate treatment of this special type of colon cancer, which is preceded by detectable inflammatory bowel disease in clinical populations.

Keywords: colitis associated cancer (CAC); extracellular matrix (ECM); immunomodulation; inflammation; matrix metalloproteinases (MMPs).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / metabolism
  • Colitis* / metabolism
  • Colitis-Associated Neoplasms* / metabolism
  • Extracellular Matrix / metabolism
  • Humans
  • Matrix Metalloproteinases* / metabolism
  • Neoplasms* / metabolism

Substances

  • Matrix Metalloproteinases

Grants and funding

This study was supported by the Young Scientists Fund of the National Natural Science Fund (81903844), the Gansu Province Science Fund for Distinguished Young Scholars (20JR10RA650), and the Outstanding Youth of the Fundamental Research Funds for the Central Universities (lzujbky-2021-ey21). This study was also supported by the Macao Science and Technology Development Fund (FDCT 007/2020/ALC and 0006/2020/AKP), Natural Science Foundation of Guangdong Province, China (2020A1515010922), Traditional Chinese Medicine Bureau of Guangdong Province, China (20201183), Shenzhen–Hong Kong-Macau S&T Program (Category C) (SGDX2020110309420200), and Research Fund of the University of Macau (CPG2023-00028-ICMS).