Loss of smooth muscle calponin results in impaired blood vessel maturation in the tumor–host microenvironment
Loss of smooth muscle calponin results in impaired blood vessel maturation in the tumor–host microenvironment
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DOI：
10.1111/j.1349-7006.2007.00452.x
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发表时间：
2007-05
期刊：
影响因子：
5.7
通讯作者：
H. Yamamura;N. Hirano;H. Koyama;Y. Nishizawà;Katsuhito Takahashi
中科院分区：
文献类型：
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作者：
H. Yamamura;N. Hirano;H. Koyama;Y. Nishizawà;Katsuhito Takahashi
恶性肿瘤细胞与局部宿主组织微环境之间的相互作用在肿瘤生长、转移及其对治疗方式的反应中起着关键作用。我们通过分析Cnn 1基因缺失的突变小鼠，研究了平滑肌钙调蛋白（Cnn 1，也称为钙调蛋白h1或碱性钙调蛋白）在体内肿瘤血管形成中的作用。在这里，我们表明宿主壁细胞中Cnn 1的缺失会阻止肿瘤血管系统的成熟。体外研究表明，血小板衍生生长因子B诱导的血管平滑肌迁移被Cnn 1缺陷下调，Cnn 1的强制表达恢复了迁移。此外，在Cnn 1缺陷小鼠中，通过抗血管内皮生长因子抗体治疗对已建立的肿瘤块的破坏显著增强。这些数据，加上正常血管的结构脆弱性是由Cnn 1基因的丢失引起的知识，表明Cnn 1在血管成熟中起着重要作用，并可能对靶向肿瘤血管系统治疗人类癌症的治疗策略产生影响。（Cancer Sci 2007; 98：757-763）
The interactions between malignant cells and the microenvironment of the local host tissue play a critical role in tumor growth, metastasis and their response to treatment modalities. We investigated the roles of smooth muscle calponin (Cnn1, also called calponin h1 or basic calponin) in the development of tumor vascul ature in vivo by analyzing mutant mice lacking the Cnn1 gene. Here we show that loss of Cnn1 in host mural cells prevents maturation of tumor vasculature. In vitro studies showed that platelet‐derived growth factor B‐induced vascular smooth muscle migration was downregulated by the Cnn1‐deficiency, and forced expression of Cnn1 restored migration. Moreover, destruction of established tumor mass by treatment with an antivascular endothelial growth factor antibody was markedly enhanced in Cnn1‐deficient mice. These data, coupled with the knowledge that structural fragility of normal blood vessels is caused by loss of the Cnn1 gene, suggest that Cnn1 plays an important role in the maturation of blood vessels, and may have implications for therapeutic strategies targeting tumor vasculature for treatment of human cancers. (Cancer Sci 2007; 98: 757–763)