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ADAM28: Another ambivalent protease in cancer

Céline Hubeau1, Natacha Rocks2, Didier Cataldo3

  • 1Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.

Cancer Letters
|August 31, 2020
PubMed

Insights

A Disintegrin And Metalloproteinase (ADAM) 28 protease has dual roles in cancer. Cancer cell-expressed ADAM28 promotes metastasis, while tumor microenvironment-derived ADAM28 offers protection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Personalized cancer therapy requires understanding molecular mechanisms of metastasis.
  • Proteolytic enzymes, particularly A Disintegrin And Metalloproteinases (ADAMs), are implicated in cancer progression.
  • ADAM28 is a metalloproteinase with known roles in cancer.

Purpose of the Study:

  • To review the distinct functions of ADAM28 based on its cellular origin (cancer cells vs. tumor microenvironment).
  • To highlight the contrasting roles of ADAM28 in cancer metastasis and immune response.
  • To propose future research directions for ADAM28 in cancer therapy.

Main Methods:

  • Literature review of studies investigating ADAM28 in various cancer contexts.
  • Analysis of experimental data from ADAM28 knockout (KO) mouse models.
  • Comparative assessment of ADAM28 functions when expressed by tumor cells versus the host microenvironment.

Main Results:

  • ADAM28 expressed by cancer cells enhances proliferation, survival, migration, and metastasis.
  • ADAM28 from the tumor microenvironment inhibits metastasis and supports T cell immune response.
  • ADAM28 KO mice exhibit accelerated lung colonization, increased tumor foci, and impaired immunity.

Conclusions:

  • ADAM28 exhibits context-dependent functions in cancer, acting as a pro-tumorigenic factor when produced by cancer cells and an anti-metastatic factor when derived from the tumor microenvironment.
  • Targeting ADAM28 offers potential for novel cancer therapeutics, depending on its source.
  • Further research is needed to fully elucidate ADAM28's multifaceted roles in cancer progression and immunity.
Keywords:
ADAM28Cancer biomarkerCell proliferationMetastasisTumor microenvironment

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