Osteopontin is an autocrine mediator of hepatocyte growth factor-induced invasive growth.
Osteopontin is an autocrine mediator of hepatocyte growth factor-induced invasive growth.
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发表时间：
2001-08
期刊：
影响因子：
11.2
通讯作者：
E. Medico;Alessandra Gentile;C. L. Celso;Tracy Ann Williams;Giovanna Gambarotta;L. Trusolino;P. M. Comoglio
中科院分区：
文献类型：
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作者：
E. Medico;Alessandra Gentile;C. L. Celso;Tracy Ann Williams;Giovanna Gambarotta;L. Trusolino;P. M. Comoglio
在上皮细胞中，肝细胞生长因子（HGF）激活涉及细胞-细胞解离（“散射”）、生长和侵袭的遗传程序。完整的程序不是由其他生长因子如表皮生长因子引起的，并且在癌症进展到侵袭转移表型期间被异常激活。为了确定参与侵袭性生长的基因，我们通过cDNA微阵列探索了小鼠胚胎肝细胞对HGF的体外转录反应。我们确定骨桥蛋白（OPN），分泌的基质蛋白，作为一个主要的肝细胞生长因子的转录目标。OPN诱导波在6 h时最大，伴随着散射的开始，并且是特异性的，因为在微阵列探索的那些基质蛋白中没有其他基质蛋白受到影响。有趣的是，HGF，而不是表皮生长因子，通过CD 44受体促进细胞与OPN的粘附。抗OPN和CD 44的抗体显著损害了散射;相反，组成性OPN过表达显著增加了对HGF的运动和侵入性反应，导致该配体触发的有序形态发生程序的破坏。
In epithelial cells, hepatocyte growth factor (HGF) activates a genetic program involving cell-cell dissociation ("scattering"), growth and invasiveness. The full program is not elicited by other growth factors like epidermal growth factor, and is aberrantly activated during cancer progression to the invasive-metastatic phenotype. To identify genes involved in the onset of invasive growth, we explored by cDNA microarrays the in vitro transcriptional response to HGF of mouse embryo liver cells. We identified osteopontin (OPN), a secreted matrix protein, as a major HGF transcriptional target. The wave of OPN induction is maximal at 6 h, in concomitance with the initiation of scattering, and is specific, because no other matrix protein among those explored by the microarray is affected. Interestingly, HGF, but not epidermal growth factor, promotes cell adhesion to OPN via the CD44 receptor. Scattering is significantly impaired by antibodies against OPN and CD44; conversely, constitutive OPN overexpression dramatically increases the motile and invasive responses to HGF, leading to disruption of the ordered morphogenetic program triggered by this ligand.