Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

Molecular Cancer

Research

Céline Sabatel¹  Ingrid Struman¹  Ludovic Malvaux¹  Karolien Castermans¹  Sébastien P Tabruyn¹  Anne M Cornet¹  Joseph A Martial¹ 

[1] Unit of Molecular Biology and Genetic Engineering, GIGA-research, University of Liège, B34, Avenue de l'Hôpital, 1, B-4000, Liège, Belgium;

关键词: Endothelial Cell;    Vascular Endothelial Growth Factor;    HCT116 Cell;    Endothelial Cell Proliferation;    siRNA Duplex;   

DOI  :  10.1186/1476-4598-9-231

 received in 2009-12-18, accepted in 2010-09-02,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundDisorganized angiogenesis is associated with several pathologies, including cancer. The identification of new genes that control tumor neovascularization can provide novel insights for future anti-cancer therapies. Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new genes. We identified SPRY1 by comparing the transcriptomes of untreated endothelial cells with those of endothelial cells treated by the angiostatic agent 16 K prolactin (16 K hPRL). In the present study, we aimed to explore the potential function of SPRY1 in angiogenesis.ResultsWe confirmed 16 K hPRL induced up-regulation of SPRY1 in primary endothelial cells. In addition, we demonstrated the positive SPRY1 regulation in a chimeric mouse model of human colon carcinoma in which 16 K hPRL treatment was shown to delay tumor growth. Expression profiling by qRT-PCR with species-specific primers revealed that induction of SPRY1 expression by 16 K hPRL occurs only in the (murine) endothelial compartment and not in the (human) tumor compartment. The regulation of SPRY1 expression was NF-κB dependent. Partial SPRY1 knockdown by RNA interference protected endothelial cells from apoptosis as well as increased endothelial cell proliferation, migration, capillary network formation, and adhesion to extracellular matrix proteins. SPRY1 knockdown was also shown to affect the expression of cyclinD1 and p21 both involved in cell-cycle regulation. These findings are discussed in relation to the role of SPRY1 as an inhibitor of ERK/MAPK signaling and to a possible explanation of its effect on cell proliferation.ConclusionsTaken together, these results suggest that SPRY1 is an endogenous angiogenesis inhibitor.

【 授权许可】

Unknown   
© Sabatel et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.