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Matrix Metalloproteinases' Role in Tumor Microenvironment.

Georgina Gonzalez-Avila1, Bettina Sommer2, A Armando García-Hernández3

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Matrix metalloproteinases (MMPs) are crucial for cancer cell evolution and metastasis within the tumor microenvironment (TME). These enzymes, secreted by various cells, drive key processes like epithelial-mesenchymal transition and tumor cell migration.

Keywords:
AcidosisAdipocyteAngiogenesisCAFsEMTHypoxiaLymphangiogenesisMMPsMast cellsMetastasisTAMsTANsTIMPsTME“Warburg effect”

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Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Biology

Background:

  • Cancer cells evolve within the tumor microenvironment (TME) through a process known as the metastatic cascade.
  • Tumor cells interact with non-neoplastic cells in the TME, co-opting them to facilitate cancer progression.
  • Key stromal cells like cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs) play significant roles.

Purpose of the Study:

  • To discuss the contribution of matrix metalloproteinases (MMPs) to cancer cell evolution.
  • To explore the cellular origins of MMPs within the tumor microenvironment.
  • To elucidate the influence of MMPs on critical processes within the TME.

Main Methods:

  • Review of scientific literature on matrix metalloproteinases (MMPs) in cancer.
  • Analysis of the role of MMPs secreted by neoplastic and stromal cells.
  • Investigation of how TME conditions like hypoxia and acidification affect MMP synthesis.

Main Results:

  • MMPs are expressed and secreted by cancer cells, CAFs, TAMs, and TANs.
  • Hypoxia and acidification in the TME induce MMP synthesis.
  • MMPs promote epithelial-mesenchymal transition (EMT), apoptosis resistance, angiogenesis, and lymphangiogenesis.
  • MMPs facilitate tumor cell migration through the basement membrane (BM) and extracellular matrix (ECM).

Conclusions:

  • Matrix metalloproteinases (MMPs) are key mediators of cancer cell evolution and metastasis.
  • MMPs orchestrate crucial events in the tumor microenvironment, enabling tumor progression.
  • Understanding MMPs' roles is vital for developing targeted cancer therapies.