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Advances in Brief

Complex Regulation of Membrane-Type Matrix Metalloproteinase Expression and Matrix Metalloproteinase-2 Activation by Concanavalin A in MDA-MB-231 Human Breast Cancer Cells

Ming Yu, Hiroshi Sato, Motoharu Seiki and Erik W. Thompson
Ming Yu
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Hiroshi Sato
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Motoharu Seiki
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Erik W. Thompson
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DOI:  Published August 1995
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Abstract

Matrix Metalloproteinase-2 (MMP-2) is secreted as a zymogen, the activation of which has been associated with metastatic progression in human breast cancer (HBC). Concanavalin A (Con A) has been found to induce activation of MMP-2 in invasive HBC cell lines. Con A effects on the expression of mRNA for membrane-type matrix metalloproteinase (MT-MMP), a newly described cell surface-associated MMP, showed a close temporal correlation with induction of MMP-2 activation. It is surprising that MT-MMP mRNA is constitutively present in the uninduced MDA-MB-231 cell, despite a lack of MMP-2 activation. We have used actinomycin D to demonstrate a partial requirement for de novo gene expression in the induction of MMP-2 activation by Con A in MDA-MB-231 HBC cells. Furthermore, this transcriptional response to Con A appeared to require the continued presence of Con A for its manifestation. The nontranscriptional component of the Con A induction manifests rapidly, is quite substantial, and persists strongly despite actinomycin D abrogation of both constitutive and Con A-induced MT-MMP. Cycloheximide analyses suggest that protein synthesis may be involved in this rapid transcription-independent response. These studies suggest that Con A induces MMP-2-activation in part by up-regulation of MT-MMP expression but has a more complicated mode of action, involving additional nontranscriptional effects, which apparently require protein synthesis.

Footnotes

  • ↵1 This work was supported in part by NIH Grant CA61344.

  • ↵2 To whom requests for reprints should be addressed, at Room W416 NRB, Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, N.W., Washington DC, 20007.

  • Received March 14, 1995.
  • Accepted June 16, 1995.
  • ©1995 American Association for Cancer Research.
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August 1995
Volume 55, Issue 15
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Complex Regulation of Membrane-Type Matrix Metalloproteinase Expression and Matrix Metalloproteinase-2 Activation by Concanavalin A in MDA-MB-231 Human Breast Cancer Cells
Ming Yu, Hiroshi Sato, Motoharu Seiki and Erik W. Thompson
Cancer Res August 1 1995 (55) (15) 3272-3277;

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Complex Regulation of Membrane-Type Matrix Metalloproteinase Expression and Matrix Metalloproteinase-2 Activation by Concanavalin A in MDA-MB-231 Human Breast Cancer Cells
Ming Yu, Hiroshi Sato, Motoharu Seiki and Erik W. Thompson
Cancer Res August 1 1995 (55) (15) 3272-3277;
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