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Matrix Metalloproteinases in the Hematopoietic Microenvironment.

A Janowska-Wieczorek1, A Matsuzaki1, L A Marquez1

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Summary

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are present in the bone marrow microenvironment. Their specific roles in normal hematopoiesis and leukemia require further investigation.

Keywords:
AMLCD34+ progenitorsMMPsTIMPsbone marrow stroma

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Hematology

Background:

  • Matrix metalloproteinases (MMPs) are enzymes that degrade extracellular matrix (ECM) and basement membranes.
  • MMPs are involved in physiological processes and pathological conditions like tumor invasion and metastasis.
  • MMP function is regulated by activation of latent forms and inhibition by tissue inhibitors of metalloproteinases (TIMPs).

Purpose of the Study:

  • To investigate the roles of MMPs and TIMPs in the bone marrow microenvironment during normal hematopoiesis and leukemia.
  • To analyze the expression and function of gelatinases (MMP-2 and MMP-9) in leukemic cells and normal hematopoietic stem/progenitor cells.

Main Methods:

  • In vitro invasion assays using reconstituted basement membrane (Matrigel).
  • Analysis of MMP/TIMP expression in normal bone marrow cells and leukemic cell lines (KG-1).
  • Assessment of MMP-2 and MMP-9 expression in bone marrow CD34(+) cells and their transmigration capabilities.

Main Results:

  • Primary acute myelogenous leukemia (AML) blasts and KG-1 cells invade Matrigel and secrete MMP-2 and MMP-9.
  • Active MMP-2 is expressed on the surface of leukemic cells.
  • Normal bone marrow CD34(+) cells lack MMP-2 and MMP-9 expression, but cytokines can induce their expression and migration.
  • MMP-2, MMP-9, TIMP-1, and TIMP-2 are produced within the bone marrow microenvironment.

Conclusions:

  • MMPs and TIMPs are components of the hematopoietic microenvironment.
  • Gelatinases play a role in leukemic cell invasion and transmigration of hematopoietic stem/progenitor cells.
  • Further research is needed to elucidate the precise functions of MMPs and TIMPs in hematopoiesis and leukemia.