TY - JOUR
T1 - The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis
AU - Oh, J.
AU - Takahashi, R.
AU - Kondo, S.
AU - Mizoguchi, A.
AU - Adachi, E.
AU - Sasahara, R. M.
AU - Nishimura, S.
AU - Imamura, Y.
AU - Kitayama, H.
AU - Alexander, D. B.
AU - Ide, C.
AU - Horan, T. P.
AU - Arakawa, T.
AU - Yoshida, H.
AU - Nishikawa, S. I.
AU - Itoh, Y.
AU - Seiki, M.
AU - Itohara, S.
AU - Takahashi, C.
AU - Noda, M. M.
N1 - 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.
PY - 2001/12/14
Y1 - 2001/12/14
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(01)00597-9
DO - 10.1016/S0092-8674(01)00597-9
M3 - Article
C2 - 11747814
AN - SCOPUS:18244367390
VL - 107
SP - 789
EP - 800
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -