Author/Authors :
Hiratsuka، نويسنده , , Sachie and Nakamura، نويسنده , , Kazuhiro and Iwai، نويسنده , , Shinobu and Murakami، نويسنده , , Masato and Itoh، نويسنده , , Takeshi and Kijima، نويسنده , , Hiroshi and Shipley، نويسنده , , J.Michael and Senior، نويسنده , , Robert M and Shibuya، نويسنده , , Masabumi، نويسنده ,
Abstract :
The molecular mechanism of tissue-specific metastasis in tumors endogenously expressing members of the vascular endothelial growth factor (VEGF) family is not yet clear. Here we demonstrate that MMP9 is specifically induced in premetastatic lung endothelial cells and macrophages by distant primary tumors via VEGFR-1/Flt-1 tyrosine kinase (TK) and that it significantly promotes lung metastasis. In a genetic approach using mice, suppression of MMP9 induction by deletion of either VEGFR-1TK or MMP9 markedly reduced lung metastasis. Furthermore, the MMP9 levels in endothelial cells of normal lung lobes from patients carrying distant tumors were significantly elevated as compared with those from patients without tumors. Thus, a block of MMP9 induction via VEGFR-1 inhibition could be useful for the prevention of tumor metastasis in lung.
