Requirement for sphingosine 1–phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference
AUTOR(ES)
Chae, Sung-Suk
FONTE
American Society for Clinical Investigation
RESUMO
Angiogenesis, or new blood vessel formation, is critical for the growth and spread of tumors. Multiple phases of this process, namely, migration, proliferation, morphogenesis, and vascular stabilization, are needed for optimal tumor growth beyond a diffusion-limited size. The sphingosine 1–phosphate (S1P) receptor-1 (S1P1) is required for stabilization of nascent blood vessels during embryonic development. Here we show that S1P1 expression is strongly induced in tumor vessels. We developed a multiplex RNA interference technique to downregulate S1P1 in mice. The small interfering RNA (siRNA) for S1P1 specifically silenced the cognate transcript in endothelial cells and inhibited endothelial cell migration in vitro and the growth of neovessels into subcutaneous implants of Matrigel in vivo. Local injection of S1P1 siRNA, but not a negative control siRNA, into established tumors inhibited the expression of S1P1 polypeptide on neovessels while concomitantly suppressing vascular stabilization and angiogenesis, which resulted in dramatic suppression of tumor growth in vivo. These data suggest that S1P1 is a critical component of the tumor angiogenic response and argue for the utility of siRNA technology in antiangiogenic therapeutics.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=522258Documentos Relacionados
- Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1-phosphate
- Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor
- Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization
- A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes.
- Sphingosine 1-phosphate activates Weibel-Palade body exocytosis