1. ¹Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
2. ²Devision of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

Correspondence: Professor MM Taketo, MD, PhD, Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo, Kyoto 606-8501, Japan. E-mail: taketo@mfour.med.kyoto-u.ac.jp

³These authors contributed equally to this work.

Received 9 July 2008; Revised 5 September 2008; Accepted 16 September 2008; Published online 10 November 2008.

Abstract

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- 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- family signaling is blocked.