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

Clin Exp Metastasis. 1999 May;17(3):205-12. doi: 10.1023/a:1006562818088.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Coculture Techniques
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Culture Media, Conditioned / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Gelatinases / biosynthesis*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / biosynthesis*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Culture Media, Conditioned
  • RNA, Messenger
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2