Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors

Angiogenesis is required for the progression of tumors from a benign to a m alignant phenotype and for metastasis. Malignant tumor cells secrete factor s such as vascular endothelial growth factor (VEGF), which bind to their co gnate receptors on endothelial cells to induce angiogenesis. Here it is sho wn that several tumor types express VEGF receptors (VEGFRs) and that inhibi tion of VEGF (VEGF antisense oligonucleotide AS-3) or VEGFFs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro. Furth ermore, this effect was abrogated by exogenous VEGF. Thus, VEGF is an autoc rine growth factor for tumor cell lines that express VEGFRs. A modified for m of VEGF AS-3 (AS-3m), in which flanking 4 nucleotides were substituted wi th 2-O-methylnucleosides (mixed backbone oil-gonucleotides), retained speci ficity and was active when given orally or systemically in vitro and in mur ine tumor models. In VEGFR-2-expressing tumors, VEGF inhibition may have du al functions: direct inhibition of tumor cell growth and inhibition of angi ogenesis.