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Dev Biol May 15, 2007; 305 (2): 599-614.
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Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis.

Kälin RE , Kretz MP , Meyer AM , Kispert A , Heppner FL , Brändli AW .

Apelin and its G protein-coupled receptor APJ play important roles in blood pressure regulation, body fluid homeostasis, and possibly the modulation of immune responses. Here, we report that apelin-APJ signaling is essential for embryonic angiogenesis and upregulated during tumor angiogenesis. A detailed expression analysis demonstrates that both paracrine and autocrine mechanisms mark areas of embryonic and tumor angiogenesis. Knockdown studies in Xenopus reveal that apelin-APJ signaling is required for intersomitic vessel angiogenesis. Moreover, ectopic expression of apelin but not vascular endothelial growth factor A (VEGFA) is sufficient to trigger premature angiogenesis. In vitro, apelin is non-mitogenic for primary human endothelial cells but promotes chemotaxis. Epistasis studies in Xenopus embryos suggest that apelin-APJ signaling functions downstream of VEGFA. Finally, we show that apelin and APJ expression is highly upregulated in microvascular proliferations of brain tumors such as malignant gliomas. Thus, our results define apelin and APJ as genes of potential diagnostic value and promising targets for the development of a new generation of anti-tumor angiogenic drugs.

PubMed ID: 17412318
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: apln aplnr erg fli1 gata3 pecam1 vegfa
GO keywords: angiogenesis [+]
Morpholinos: apln MO4 aplnr MO3 vegfa MO2

Disease Ontology terms: cancer [+]
Phenotypes: Xla Wt + apln (Fig. 3 C) [+]

Article Images: [+] show captions