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Publication : Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis.

First Author  Yang XM Year  2010
Journal  Biochem Biophys Res Commun Volume  396
Issue  2 Pages  571-7
PubMed ID  20438712 Mgi Jnum  J:162506
Mgi Id  MGI:4819069 Doi  10.1016/j.bbrc.2010.04.152
Citation  Yang XM, et al. (2010) Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis. Biochem Biophys Res Commun 396(2):571-7
abstractText  The Slit family of guidance cues binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit-Robo signaling had been reported to function as chemoattractive signal for vascular endothelial cells during angiogenesis. In this study, we found that Robo1 was expressed in lymphatic endothelial cells to mediate the migration and tube formation of these cells upon Slit2 stimulation, which were specifically inhibited by the function-blocking antibody R5 to Slit2/Robo1 interaction. To further explore the lymphangiogenic effect and significance mediated by Slit-Robo signaling, we intercrossed Slit2 transgenic mice with a non-metastatic RIP1-Tag2 mouse tumor model, and found that transgenic overexpression of Slit2 significantly enhanced tumor lymphangiogenesis and subsequently promoted mesenteric lymph node metastasis of pancreatic islet tumors. Taken together, our findings reveal that through interacting with Robo1, Slit2 is a novel and potent lymphangiogenic factor and contributes to tumor lymphatic metastasis.
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