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Evidence for tumor-host cooperation in regulating MMP-2 expression in human colon cancer

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Abstract

Matrix metalloproteinase 2 (MMP-2) facilitates tumor growth and metastasis in colon cancer. Although tumor cells may produce MMP-2, stromal cells, such as macrophages and fibroblasts, contribute significantly to MMP-2 synthesis in human tumors. We characterized four human colon cancer cell lines with differing biological behavior for MMP-2 expression. While the parent tumors from which the cell lines were derived all expressed MMP-2 mRNA, MMP-2 transcripts were detected in only one cell line, TF-17C, which is nontumorigenic in a nude mouse tumor model. TF-43C, which is tumorigenic and metastatic in the same tumor model, did not produce MMP-2, yet the tumors which arose from it after injection into nude mice did contain MMP-2 mRNA, suggesting a contribution from stromal cells. Co-culturing TF-43C with fibroblasts resulted in an increase in MMP-2 protein, whereas co-culturing with the nontumorigenic cell line TF-13Cm did not alter constitutive fibroblast MMP-2 secretion. Conditioned medium from TF-43C cells also stimulated fibroblast MMP-2 production. These data suggest that a soluble factor from TF-43C cells can stimulate fibroblast MMP-2 production and support the hypothesis that colon cancer cell interactions with stromal fibroblasts may be important determinants of tumor behavior in vivo.

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Authors and Affiliations

  1. VA Medical and Regional Office Center, White River Junction, Vermont , 05009

    Deborah L. Ornstein & Judy MacNab

  2. Department of Medicine and Surgery, Dartmouth Medical School, Hanover, NH 03755, USA

    Kenneth H. Cohn

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  1. Deborah L. Ornstein
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  2. Judy MacNab
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  3. Kenneth H. Cohn
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Ornstein, D.L., MacNab, J. & Cohn, K.H. Evidence for tumor-host cooperation in regulating MMP-2 expression in human colon cancer. Clin Exp Metastasis 17, 205–212 (1999). https://doi.org/10.1023/A:1006562818088

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