Abstract
Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.
Original language | English |
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Pages (from-to) | 789-800 |
Number of pages | 12 |
Journal | Cell |
Volume | 107 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2001 Dec 14 |
Bibliographical note
Funding Information:We thank M. Hooper for the E14 ES cells, Thomas N. Sato for the protocol for whole-mount immunostaining, Masatoshi Maki for technical advice, Ryoichi Nemori (FUJIFILM) for the FIZ materials, Emi Nishimoto and Takashi Kawai for technical assistance, and Aki Miyazaki for secretarial assistance. We are also grateful to Drs. Yoji Ikawa and Haruo Sugano for generous support and encouragement and to Drs. Robert A. Weinberg and Rudolf Jaenisch for discussion. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan to C.T. and M.N. and from Amgen, Sankyo, Co. Ltd., and Takeda Science Foundation to M.N.
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology