Tumor growth and angiogenesis is impaired in CIB1 knockout mice.

Mohamed A Zayed, Weiping Yuan, Dan Chalothorn, James E Faber, Leslie V Parise
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引用次数: 24

Abstract

Background: Pathological angiogenesis contributes to various ocular, malignant, and inflammatory disorders, emphasizing the need to understand this process more precisely on a molecular level. Previously we found that CIB1, a 22 kDa regulatory protein, plays a critical role in endothelial cell function, angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2 expression, and in vivo ischemia-induced angiogenesis. Since pathological angiogenesis is highly dependent on many of these same processes, we hypothesized that CIB1 may also regulate tumor-induced angiogenesis.

Methods: To test this hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma cells into WT and CIB1-KO mice, and monitored tumor growth, morphology, histology, and intra-tumoral microvessel density.

Results: Allografted melanoma tumors that developed in CIB1-KO mice were smaller in volume, had a distinct necrotic appearance, and had significantly less intra-tumoral microvessel density. Similarly, allografted Lewis lung carcinoma tumors in CIB1-KO mice were smaller in volume and mass, and appeared to have decreased perfusion. Intra-tumoral hemorrhage, necrosis, and perivascular fibrosis were also increased in tumors that developed in CIB1-KO mice.

Conclusions: These findings suggest that, in addition to its other functions, CIB1 plays a critical role in facilitating tumor growth and tumor-induced angiogenesis.

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在CIB1敲除小鼠中,肿瘤生长和血管生成受到损害。
背景:病理性血管生成有助于各种眼部、恶性和炎症性疾病,强调需要在分子水平上更精确地理解这一过程。先前我们发现CIB1是一个22 kDa的调节蛋白,在内皮细胞功能、血管生成生长因子介导的细胞功能、PAK1激活、MMP-2表达和体内缺血诱导的血管生成中起关键作用。由于病理性血管生成高度依赖于许多相同的过程,我们假设CIB1也可能调节肿瘤诱导的血管生成。方法:为了验证这一假设,我们将小鼠B16黑色素瘤或Lewis肺癌细胞同种异体移植到WT和CIB1-KO小鼠体内,并监测肿瘤生长、形态学、组织学和肿瘤内微血管密度。结果:在CIB1-KO小鼠中发生的同种异体移植黑色素瘤肿瘤体积较小,具有明显的坏死外观,肿瘤内微血管密度明显降低。同样,同种异体移植的CIB1-KO小鼠Lewis肺癌肿瘤体积和质量较小,灌注减少。在CIB1-KO小鼠中,肿瘤内出血、坏死和血管周围纤维化也增加。结论:这些发现表明,除了其其他功能外,CIB1在促进肿瘤生长和肿瘤诱导的血管生成中起着关键作用。
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