Gene expression profiling of the tumor angiogenic switch in Rip1Tag2 mice. Mus musculus

Angiogenesis represents a rate-limiting step during tumor progression. Molecular mechanisms driving tumor angiogenesis (e.g. implicating signaling by VEGFs and their receptors) have been elucidated and allowed to design targeted therapies. However, limits of such anti-angiogenic therapies have emerged, notably because tumor cells adapt and tumors recur in more aggressive fashions. There is therefore a need to identify novel mechanisms implicated in tumor angiogenesis that have a potential towards translational applications. Using a transgenic murine model of pancreatic neuroendocrine cancer (Hanahan, Nature 315, 1985) where angiogenesis represents an early and discrete step of multi-stage tumor progression (Folkman et al. , Nature 339, 1989), we compared non-angiogenic and angiogenic early tumors to obtain a comprehensive description of the tumor angiogenic switch at the level of gene expression. Overall design: Early tumor islets from 8 weeks old Rip1Tag2 mice were differentially isolated to compare the transcriptome of angiogenic versus non-angiogenic islets.