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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

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

Authors: Céline Sabatel, Anne M Cornet, Sébastien P Tabruyn, Ludovic Malvaux, Karolien Castermans, Joseph A Martial, Ingrid Struman

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Disorganized 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.

Results

We 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.

Conclusions

Taken together, these results suggest that SPRY1 is an endogenous angiogenesis inhibitor.
Appendix
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Metadata
Title
Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis
Authors
Céline Sabatel
Anne M Cornet
Sébastien P Tabruyn
Ludovic Malvaux
Karolien Castermans
Joseph A Martial
Ingrid Struman
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-231

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