Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas.
Expression of matrix metalloproteinase 7 (MMP7) is increased in the human colorectal carcinomas, and correlates with malignant progression. However, its contribution to colon cancer pathogenesis is not understood thoroughly. To investigate the roles of MMP7 in colon cancer progression, we introduced an Mmp7 knockout mutation into the cis-Apc/Smad4 mutant mouse, a model of invasive colon cancer in which SMAD4-dependent TGF-beta family signaling is inactivated. We demonstrate here that lack of MMP7 reduces the number and size of tumors in the cis-Apc/Smad4 mice. On the other hand, MMP7-deficiency does not affect the depth of tumor invasion, number of stromal fibroblasts or levels of extracellular matrix components in the tumors. These results indicate that MMP7 is required for tumor formation, but not for the invasion or fibrosis of the colon cancer whose SMAD4-dependent TGF-beta family signaling is blocked.
Kitamura
Takanori
T
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Biyajima
Kyoko
K
Aoki
Masahiro
M
Oshima
Masanobu
M
Taketo
Makoto M
MM
D000230:Adenocarcinoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D017491:Genes, APC; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D051901:Smad4 Protein / Q000172:deficiency*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D024042:Collagen Type I; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D020783:Matrix Metalloproteinase 7