Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis

	Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis
	Wang, LJ; Zhao, Y; Han, B; Ma, YG; Zhang, J; Yang, DM; Mao, JW; Tang, FT; Li, WD; Yang, Y
刊名	CANCER SCIENCE
	2008
卷号	99 期号:3 页码:510-517
通讯作者	Wang, R (reprint author), Lanzhou Univ, Sch Stomatol, Sch Life Sci, Dept Biochem & Mol Biol, Lanzhou 730000, Peoples R China.,wangrui@lzu.edu.cn ; gengx011@umn.edu
英文摘要	Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a repellent for axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. We have previously shown that Slit2 is also secreted by a variety of human cancer cells whereby it acts as a chemoattractant to vascular endothelial cells for tumor angiogenesis. We used a blocking antibody to investigate the role of Slit-Robo signaling in tumor angiogenesis during oral carcinogenesis. In this report we undertook a multistage model of 7,12-dimethyl-1,2-benzanthracene-induced squamous cell carcinoma in the hamster buccal pouch. R5, a monoclonal antibody against the first immunoglobulin domain of Robo1, was used to study whether R5 blocks the Slit-Robo interaction and furthermore inhibits tumor angiogenesis and growth in our model. In addition, the expression of Slit2, von Willebrand factor, and vascular endothelial growth factor were examined using human tissue of oral cheek mucosa with oral squamous cell carcinoma. Our data showed that Slit2 was expressed minimally in normal and hyperplastic mucosa, moderately in dysplastic mucosa, and highly in neoplastic mucosa obtained from hamster buccal pouch. We also found that increased Slit2 expression was associated with higher tumor angiogenesis, as reflected by increased vascular endothelial growth factor expression and microvessel density. A similar Slit2 expression profile was found in human tissue. Importantly, interruption of the Slit2-Robo interaction using R5 inhibited tumor angiogenesis and growth in our in vivo model, which indicates that Slit2-mediated tumor angiogenesis is a critical process underlying the carcinogenesis of chemical-induced squamous cell carcinoma. Therefore, targeting Slit-Robo signaling may offer a novel antiangiogenesis approach for oral cancer therapy.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	ENDOTHELIAL GROWTH-FACTOR ; AXON GUIDANCE ; NEURONAL MIGRATION ; COLORECTAL-CANCER ; VERTEBRATE SLIT ; ROBO GENES ; EXPRESSION ; RECEPTORS ; PROTEINS ; PROGRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000252983200009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1358]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, LJ,Zhao, Y,Han, B,et al. Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis[J]. CANCER SCIENCE,2008,99(3):510-517.
APA	Wang, LJ.,Zhao, Y.,Han, B.,Ma, YG.,Zhang, J.,...&Geng, JG.(2008).Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis.CANCER SCIENCE,99(3),510-517.
MLA	Wang, LJ,et al."Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis".CANCER SCIENCE 99.3(2008):510-517.