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 |
|---|---|
| Pages (from-to) | 789-800 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 107 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2001 Dec 14 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. / Oh, Jun Seo; Takahashi, R.; Kondo, S.; Mizoguchi, A.; Adachi, E.; Sasahara, R. M.; Nishimura, S.; Imamura, Y.; Kitayama, H.; Alexander, D. B.; Ide, C.; Horan, T. P.; Arakawa, T.; Yoshida, H.; Nishikawa, S. I.; Itoh, Y.; Seiki, M.; Itohara, S.; Takahashi, C.; Noda, M. M.
In: Cell, Vol. 107, No. 6, 14.12.2001, p. 789-800.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis
AU - Oh, Jun Seo
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.
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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UR - http://www.scopus.com/inward/citedby.url?scp=18244367390&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00597-9
DO - 10.1016/S0092-8674(01)00597-9
M3 - Article
VL - 107
SP - 789
EP - 800
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -