Impaired tumor angiogenesis and VEGF-induced pathway in endothelial CD146 knockout mice.
Impaired tumor angiogenesis and VEGF-induced pathway in endothelial CD146 knockout mice.
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内皮 CD146 敲除小鼠中肿瘤血管生成和 VEGF 诱导途径受损
DOI：
10.1007/s13238-014-0047-y
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发表时间：
2014-06
期刊：
影响因子：
21.1
通讯作者：
Yan, Xiyun
中科院分区：
文献类型：
--
作者：
Zeng, Qiqun;Wu, Zhenzhen;Duan, Hongxia;Jiang, Xuan;Tu, Tao;Lu, Di;Luo, Yongting;Wang, Ping;Song, Lina;Feng, Jing;Yang, Dongling;Yan, Xiyun
CD 146是一种新发现的内皮生物标志物，与血管生成有关。CD 146的促血管生成作用已被广泛报道，但尚缺乏体内证据。为了解决这个问题，我们使用Tg（Tek-cre）系统产生内皮特异性CD 146敲除（CD 146 EC-KO）小鼠。令人惊讶的是，这些小鼠在正常视网膜血管系统的发育中没有表现出任何明显的形态学缺陷。为了评估CD 146在病理性血管生成中的作用，使用异种移植肿瘤模型。我们发现，与WT同窝小鼠相比，CD 146 EC-KO小鼠的肿瘤体积和血管密度均显著降低。此外，CD 146 EC-KO小鼠的内皮细胞（EC）对VEGF处理的发芽、迁移和管形成能力受损。机制研究进一步证实VEGF诱导的VEGFR-2磷酸化和AKT/p38 MAPK/NF-κB活化在这些CD 146-null EC中受到抑制，这可能是观察到的CD 146 EC-KO小鼠肿瘤血管生成抑制的潜在原因。这些结果表明，CD 146在生理性血管生成过程中起着多余的作用，但在肿瘤发生中观察到的病理性血管生成过程中变得至关重要。
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Thoughin vitroangiogenic function of CD146 has been extensively reported,in vivoevidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146EC-KO) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146EC-KOmice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146EC-KOmice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146EC-KOmice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
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影响因子：
4.2
作者：
Kohama, K;Tsukamoto, Y;Taira, E
通讯作者：
Taira, E
影响因子：
4.8
作者：
Hirata, K;Ishida, T;Quertermous, T
通讯作者：
Quertermous, T
DOI：
10.1111/j.1749-6632.2009.04967.x
发表时间：
2009-01-01
期刊：
HEMATOPOIETIC STEM CELLS VII
影响因子：
--
作者：
Crisan, Mihaela;Chen, Chien-Wen;Peault, Bruno
通讯作者：
Peault, Bruno
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
15.9
作者：
Graesser, D;Solowiej, A;Madri, JA
通讯作者：
Madri, JA