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Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma cells

K Takahashi1, H Eto, K K Tanabe

  • 1Department of Surgery, Massachusetts General Hospital, Boston 02114, USA.

International Journal of Cancer
|February 6, 1999
PubMed

Insights

Targeting CD44 with the F10-44-2 antibody up-regulates matrix metalloproteinase-2 (MMP-2), enhancing melanoma cell migration and invasion. This suggests a novel mechanism for controlling cancer metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • CD44, a cell-surface adhesion protein, is implicated in cancer invasion and metastasis.
  • The precise mechanisms by which CD44 influences these processes remain unclear.

Purpose of the Study:

  • To investigate how CD44 expression affects melanoma cell invasion and metastasis.
  • To elucidate the role of CD44-mediated signaling in matrix metalloproteinase-2 (MMP-2) regulation.

Main Methods:

  • Human melanoma cells were treated with a CD44 monoclonal antibody (MAb), F10-44-2.
  • MMP-2 protein and mRNA levels were quantified.
  • Cell migration and invasion assays were performed using gelatin-coated and reconstituted basement membranes.

Main Results:

  • Treatment with F10-44-2 MAb induced significant up-regulation of MMP-2 protein and mRNA in melanoma cells.
  • Melanoma cell migration and invasion were enhanced following treatment with F10-44-2 MAb.
  • Known CD44 ligands did not induce MMP-2 production, indicating a specific antibody-mediated effect.

Conclusions:

  • CD44 binding by the F10-44-2 MAb triggers MMP-2 expression.
  • This MMP-2 induction is directly associated with enhanced melanoma cell migration and invasion.
  • Findings provide insights into tumor metastasis, development, and lymphocyte function.

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