Evidence for tumor-host cooperation in regulating MMP-2 expression in human colon cancer.
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.
Ornstein
D L
DL
VA Medical and Regional Office Center, White River Junction, Vermont 05009, USA.
MacNab
J
J
Cohn
K H
KH
D000818:Animals; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D018093:Gelatinases / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2