Collagen induced MMP-2 activation in human breast cancer

Thompson, E.W., Yu, M., Bueno, J., Jin, L., Maiti, S.N., Palao-Marco, F.L., Pulyaeva, H., Tamborlane, J.W., Tirgari, R., Wapnir, I., & Azzam, H. (1994) Collagen induced MMP-2 activation in human breast cancer. Breast Cancer Research and Treatment, 31(2-3), pp. 357-370.

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Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen(TM): Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP- 2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.

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ID Code: 71748
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):35
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 7881112
Additional URLs:
Keywords: activation, collagen, collagenase, desmoplasia, integrin, invasion, tumor, stromal interaction
DOI: 10.1007/BF00666168
ISSN: 1573-7217
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 16 May 2014 04:03
Last Modified: 16 May 2014 04:03

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