MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis
MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis
复制标题
DOI：
10.1016/s1535-6108(02)00153-8
复制
发表时间：
2002-10-01
期刊：
影响因子：
50.3
通讯作者：
Shibuya, M
中科院分区：
文献类型：
--
作者：
Hiratsuka, S;Nakamura, K;Shibuya, M
内源性表达血管内皮生长因子（VEGF）家族成员的肿瘤组织特异性转移的分子机制尚不清楚。在这里，我们证明，MMP 9特异性诱导转移前肺内皮细胞和巨噬细胞的远处原发性肿瘤通过VEGFR-1/Flt-1酪氨酸激酶（TK），它显着促进肺转移。在使用小鼠的遗传方法中，通过缺失VEGFR-1 TK或MMP 9来抑制MMP 9诱导显著减少肺转移。此外，与来自无肿瘤患者的内皮细胞相比，来自携带远处肿瘤的患者的正常肺叶的内皮细胞中MMP 9水平显著升高。因此，通过VEGFR-1抑制阻断MMP 9诱导可用于预防肺中的肿瘤转移。
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.