Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity

Biao Wang; Yang Xiao; Bei Bei Ding; Na Zhang; Xiao Bin Yuan; Lü Gui; Kai Xian Qian; Shumin Duan; Zhengjun Chen; Yi Rao; Jian Guo Geng

doi:10.1016/S1535-6108(03)00164-8

Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity

Biao Wang, Yang Xiao, Bei Bei Ding, Na Zhang, Xiao Bin Yuan, Lü Gui, Kai Xian Qian, Shumin Duan, Zhengjun Chen, Yi Rao, Jian Guo Geng^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

363 Scopus citations

Abstract

Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. Here we show Slit2 expression in a large number of solid tumors and Robo1 expression in vascular endothelial cells. Recombinant Slit2 protein attracted endothelial cells and promoted tube formation in a Robo1- and phosphatidylinositol kinase-dependent manner. Neutralization of Robo1 reduced the microvessel density and the tumor mass of human malignant melanoma A375 cells in vivo. These findings demonstrate the angiogenic function of Slit-Robo signaling, reveal a mechanism in mediating the crosstalk between cancer cells and endothelial cells, and indicate the effectiveness of blocking this signaling pathway in treating cancers.

Original language	English
Pages (from-to)	19-29
Number of pages	11
Journal	Cancer Cell
Volume	4
Issue number	1
DOIs	https://doi.org/10.1016/S1535-6108(03)00164-8
State	Published - 1 Jul 2003
Externally published	Yes

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10.1016/S1535-6108(03)00164-8

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title = "Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity",

abstract = "Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. Here we show Slit2 expression in a large number of solid tumors and Robo1 expression in vascular endothelial cells. Recombinant Slit2 protein attracted endothelial cells and promoted tube formation in a Robo1- and phosphatidylinositol kinase-dependent manner. Neutralization of Robo1 reduced the microvessel density and the tumor mass of human malignant melanoma A375 cells in vivo. These findings demonstrate the angiogenic function of Slit-Robo signaling, reveal a mechanism in mediating the crosstalk between cancer cells and endothelial cells, and indicate the effectiveness of blocking this signaling pathway in treating cancers.",

author = "Biao Wang and Yang Xiao and Ding, \{Bei Bei\} and Na Zhang and Yuan, \{Xiao Bin\} and L{\"u} Gui and Qian, \{Kai Xian\} and Shumin Duan and Zhengjun Chen and Yi Rao and Geng, \{Jian Guo\}",

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doi = "10.1016/S1535-6108(03)00164-8",

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T1 - Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity

AU - Wang, Biao

AU - Xiao, Yang

AU - Ding, Bei Bei

AU - Zhang, Na

AU - Yuan, Xiao Bin

AU - Gui, Lü

AU - Qian, Kai Xian

AU - Duan, Shumin

AU - Chen, Zhengjun

AU - Rao, Yi

AU - Geng, Jian Guo

PY - 2003/7/1

Y1 - 2003/7/1

N2 - Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. Here we show Slit2 expression in a large number of solid tumors and Robo1 expression in vascular endothelial cells. Recombinant Slit2 protein attracted endothelial cells and promoted tube formation in a Robo1- and phosphatidylinositol kinase-dependent manner. Neutralization of Robo1 reduced the microvessel density and the tumor mass of human malignant melanoma A375 cells in vivo. These findings demonstrate the angiogenic function of Slit-Robo signaling, reveal a mechanism in mediating the crosstalk between cancer cells and endothelial cells, and indicate the effectiveness of blocking this signaling pathway in treating cancers.

AB - Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. Here we show Slit2 expression in a large number of solid tumors and Robo1 expression in vascular endothelial cells. Recombinant Slit2 protein attracted endothelial cells and promoted tube formation in a Robo1- and phosphatidylinositol kinase-dependent manner. Neutralization of Robo1 reduced the microvessel density and the tumor mass of human malignant melanoma A375 cells in vivo. These findings demonstrate the angiogenic function of Slit-Robo signaling, reveal a mechanism in mediating the crosstalk between cancer cells and endothelial cells, and indicate the effectiveness of blocking this signaling pathway in treating cancers.

UR - https://www.scopus.com/pages/publications/10744224816

U2 - 10.1016/S1535-6108(03)00164-8

DO - 10.1016/S1535-6108(03)00164-8

M3 - 文章

C2 - 12892710

AN - SCOPUS:10744224816

SN - 1535-6108

VL - 4

SP - 19

EP - 29

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity

Abstract

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