Impaired tumor angiogenesis and VEGF- induced pathway in endothelial CD146 knockout mice

• Published in: Protein & cell Vol. 5; no. 6; pp. 445 - 456
• Main Authors: Zeng, Qiqun, Wu, Zhenzhen, Duan, Hongxia, Jiang, Xuan, Tu, Tao, Lu, Di, Luo, Yongting, Wang, Ping, Song, Lina, Feng, Jing, Yang, Dongling, Yan, Xiyun
• Format: Journal Article
• Language: English
• Published: Beijing Higher Education Press 01.06.2014; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; CD146 Antigen - genetics; CD146 Antigen - metabolism; Cell Biology; Cells, Cultured; Developmental Biology; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; Human Genetics; Life Sciences; Male; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Physiologic - drug effects; NF-kappa B - metabolism; NF-KB; Phosphorylation - drug effects; Protein Science; Proto-Oncogene Proteins c-akt - metabolism; Research Article; Retinal Vein - growth & development; Retinal Vein - pathology; Signal Transduction - drug effects; Stem Cells; Transplantation, Homologous; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGF; 内皮细胞; 基因敲除; 小鼠; 肿瘤血管生成; 诱导; 通路; knockout mice; CD146; VEGF; tumor angiogenesis
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-014-0047-y

CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angio- genic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout （CD146 EC-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-KO mice 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-Ko mice. Mechanistic studies further confirmed that VEGF- induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/ NF-KB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146Ec-Ko mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.