Collagen-induced activation of the M(r) 72,000 type IV collagenase in normal and malignant human fibroblastoid cells.
Although the M(r) 72,000 type IV collagenase (matrix metalloproteinase 2) has been implicated in a variety of normal and pathogenic processes, its activation mechanism in vivo is unclear. We have found that fibroblasts from normal and neoplastic human breast, as well as the sarcomatous human Hs578T and HT1080 cell lines, activate endogenous matrix metalloprotease 2 when cultured on type I collagen gels, but not on plastic, fibronectin, collagen IV, gelatin, matrigel, or basement membrane-like HR9 cell matrix. This activation is monitored by the zymographic detection of M(r) 59,000 and/or M(r) 62,000 species, requires 2-3 days of culture on vitrogen to manifest, is cycloheximide inhibitable, and correlates with an arborized morphology. A similar activation pattern was seen in these cells in response to Concanavalin A but not transforming growth factor beta or 12-O-tetradecanoylphorbol-13-acetate. The interstitial matrix may thus play an important role in regulating matrix degradation in vivo.
Azzam
H S
HS
Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.
Thompson
E W
EW
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002296:Carcinosarcoma / Q000201:enzymology* / Q000473:pathology; D003094:Collagen / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D004790:Enzyme Induction; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9; D003012:Microbial Collagenase / Q000096:biosynthesis* / Q000737:chemistry; D008970:Molecular Weight; D010662:Phenylmercuric Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003208:Concanavalin A; C010024:4-aminophenylmercuriacetate; D003094:Collagen; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate; D010662:Phenylmercuric Acetate