Author/Authors :
Junseo Oh، نويسنده , , Rei Takahashi، نويسنده , , Shunya Kondo، نويسنده , , Akira Mizoguchi، نويسنده , , Eijiro Adachi، نويسنده , , Regina M. Sasahara، نويسنده , , Sachiko Nishimura، نويسنده , , Yukio Imamura، نويسنده , , Hitoshi Kitayama، نويسنده , , David B. Alexander، نويسنده , , Chizuka Ide، نويسنده , , Thomas P. Horan، نويسنده , , Tsutomu Arakawa، نويسنده , , Hisahito Yoshida، نويسنده , , Shin-Ichi Nishikawa، نويسنده , , Yoshifumi Itoh، نويسنده , , Motoharu Seiki، نويسنده , , Shigeyoshi Itohara، نويسنده , , Chiaki Takahashi، نويسنده , , Makoto Noda، نويسنده , , et al.، نويسنده ,
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.
