Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression
Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression
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DOI：
10.1128/mcb.24.9.3992-4003.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Wang, XF
中科院分区：
文献类型：
--
作者：
Shao, R;Bao, SD;Wang, XF
人类乳腺癌发展的后期阶段是人们很难理解的复杂过程，与癌症基因的表达有关，这些基因促进了特定的致癌活动，如血管生成。在这里，我们描述了Periostin是一种间充质特异性基因，其在人类乳腺癌中的获得性表达导致肿瘤进展和血管生成的显著增强。在正常的人类乳腺组织中检测不到Periostin，发现在所研究的绝大多数人类原发乳腺癌中Periostin过表达。基因工程过表达Periostin的肿瘤细胞系在免疫功能受损的动物体内移植时，表现出加速生长和血管生成的表型。Periostin诱导血管生成的潜在机制被发现部分源于内皮细胞通过整合素α(V)-β(3)-粘着斑激酶介导的信号通路上调血管内皮生长因子受体Flk-1/KDR。这些发现表明，在肿瘤发生的晚期阶段，通过表达间充质特异性基因获得肿瘤血管生成的新机制是至关重要的一步。
The late stages of human breast cancer development are poorly under-stood complex processes associated with the expression of genes by cancers that promote specific tumorigenic activities, such as angiogenesis. Here, we describe the identification of periostin as a mesenchyme-specific gene whose acquired expression by human breast cancers leads to a significant enhancement in tumor progression and angiogenesis. Undetectable in normal human breast tissues, periostin was found to be overexpressed by the vast majority of human primary breast cancers examined. Tumor cell lines engineered to overexpress periostin showed a phenotype of accelerated growth and angiogenesis as xenografts in immunocompromised animals. The underlying mechanism of periostin-mediated induction of angiogenesis was found to derive in part from the up-regulation of the vascular endothelial growth factor receptor Flk-1/KDR by endothelial cells through an integrin alpha(v)beta(3)-focal adhesion kinase-mediated signaling pathway. These findings demonstrate the presence of I novel mechanism by which tumor angiogenesis is acquired with the expression of a mesenchyme-specific gene as a crucial step in late stages of tumorigenesis.