The differential roles of Slit2-exon 15 splicing variants in angiogenesis and HUVEC permeability.

doi:10.1007/s10456-015-9467-4

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 期刊論文 > Item 310902500/11420

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11420

Title:	The differential roles of Slit2-exon 15 splicing variants in angiogenesis and HUVEC permeability.
Authors:	Yang, YC Chen, PN Wang, SY Liao, CY Lin, YY Sun, SR Chiu, CL Hsieh, YS Shieh, JC Chang, JT
Contributors:	醫學研究所
Keywords:	Slit2 splicing variants;Human umbilical vein endothelial cells;Angiogenesis;Chicken chorioallantoic membrane assay;Tube formation;Permeability;Robo1;Robo4
Date:	2015
Issue Date:	2015-07-21T03:44:12Z (UTC)
ISSN:	0969-6970
Abstract:	Slit2, a secreted glycoprotein, is down-regulated in many cancers. Slit2/Robo signaling pathway plays an important, but controversial, role in angiogenesis. We identified splicing variants of Slit2 at exon 15, Slit2-WT and Slit2-ΔE15, with differential effects on proliferation and invasive capability of lung cancer cells. The aim of this study was to elucidate the differential roles of these exon 15 splicing variants in angiogenesis. Our results revealed that both Slit2-WT and Slit2-ΔE15 inhibit motility of human umbilical vein endothelial cells (HUVECs). The conditioned medium (CM) collected from CL1-5/VC or CL1-5/Slit2-WT lung adenocarcinoma cells blocked HUVEC tube formation and angiogenesis on chorioallantoic membrane (CAM) assay when compared with untreated HUVECs and CAM, respectively. However, CM of CL1-5/Slit2-ΔE15 restored the quality of tubes and the size of vessels. Although both Slit2-WT and Slit2-ΔE15 inhibited permeability induced by CM of cancer cells, Slit2-ΔE15 exhibited stronger effect. These results suggested that Slit2-ΔE15 plays important roles in normalization of blood vessels by enhancing tube quality and tightening endothelial cells, while Slit2-WT only enhances tightening of endothelial cells. It appears that Robo4 is responsible for Slit2 isoform-mediated inhibition of permeability, while neither Robo1 nor Robo4 is required for Slit2-ΔE15-enhanced tube quality. The results of this study suggest that Slit2-ΔE15 splicing form is a promising molecule for normalizing blood vessels around a tumor, which, in turn, may increase efficacy of chemotherapy and radiotherapy.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/11420 http://dx.doi.org/10.1007/s10456-015-9467-4
Relation:	Angiogenesis. 2015 Jul;18(3):301-12.
Appears in Collections:	[生化微生物免疫研究所] 期刊論文

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