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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Wang B,Xiao Y,Ding BB,Zhang N,Yuan Xb,Gui L,Qian KX,Duan S,Chen Z,Rao Y,Geng JG

doi

10.1016/s1535-6108(03)00164-8

keywords:

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

19-29

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535610803001648

journal_volume

4

pub_type

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