Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors

  • Authors:
    • O SanchezSweatman
    • F Soares
    • M Whaley
    • R Khokha
    • F Orr
    • G Singh
  • View Affiliations

  • Published online on: December 1, 1997     https://doi.org/10.3892/ijo.11.6.1321
  • Pages: 1321-1326
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Abstract

Matrix degradation by cancer cells is an important attribute of malignant behaviour. We have postulated that during invasion and metastasis, matrix metalloproteinase (MMP) production by cancer cells is modulated by microenvironmental factors. To determine this, we screened human cancer cell lines of diverse histogenesis for their secreted MMP profile following exposure to a diversity of soluble and insoluble agents. Enzymatic changes were observed in the presence of phorbol ester (TPA) and hydrogen peroxide (H2O2). More specifically, we observed: (a) increased secretion and/or activation of gelatinases A (MMP-2) and B (MMP-9) after exposure of 8 cell lines to 10(-6) M TPA; (b) increased activation of interstitial collagenase (MMP-1) caseinolysis after stimulation of 3 cancer cell lines with 10(-7) M TPA; and (c) increased activation of MMP-2 after exposure of 2 cell lines to 0.5 mM H3O2. In functional assays, exposure of lung Calu-6 carcinoma cells to 0.5 mM H2O2 and PC-3 cells to TPA, increased their ability to degrade radiolabelled endothelial cell-derived and osteoblast-like-derived basement membranes, respectively. RNA hybridization studies confirmed and further documented these observations. We conclude that modulation of MMP activity in human cancer cells is a common phenomenon regardless of lineage. Modulatory mechanisms such as increased de novo pro-enzyme synthesis and/or release, and enhanced proenzyme activation may be involved. Furthermore, our results provide evidence that extracellular matrix degradation by human cancer cells during invasion and metastasis may be stimulated by soluble matrix-derived factors in a cell type-specific fashion.

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December 1997
Volume 11 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
SanchezSweatman O, Soares F, Whaley M, Khokha R, Orr F and Singh G: Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors. Int J Oncol 11: 1321-1326, 1997
APA
SanchezSweatman, O., Soares, F., Whaley, M., Khokha, R., Orr, F., & Singh, G. (1997). Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors. International Journal of Oncology, 11, 1321-1326. https://doi.org/10.3892/ijo.11.6.1321
MLA
SanchezSweatman, O., Soares, F., Whaley, M., Khokha, R., Orr, F., Singh, G."Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors". International Journal of Oncology 11.6 (1997): 1321-1326.
Chicago
SanchezSweatman, O., Soares, F., Whaley, M., Khokha, R., Orr, F., Singh, G."Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors". International Journal of Oncology 11, no. 6 (1997): 1321-1326. https://doi.org/10.3892/ijo.11.6.1321