VEGF, VEGF-B, VEGF-C, and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa

Because the crucial role of angiogenesis has been demonstrated in tumor gro wth and metastasis, the present study was undertaken to characterize the re lative expression of vascular endothelial growth factors VEGF (vascular end othelial growth factor), VEGF-B, VEGF-C, and their receptors KDR (kinase in sert domain-containing receptor), FLT-1 (fms-like tyrosine kinase), and FLT -4 in human colonic cancers, in relation to the Astler-Coller pathological classification, and to prognosis. VEGF and VEGF-B gene expression was quant ified by Northern blot in 72 tumor samples matched with control tissues. VE GF gene expression was 1.4 times higher in adenocarcinomas than in control tissues (p = 0.02), but did not increase further between Astler-Coller tumo r stages A and D, and did not correlate with disease recurrence for patient s at stages B2 or C. In adenomas, VEGF mRNA levels were not significantly d ifferent from those in the paired control colonic mucosa. The expression pa ttern of VEGF isoforms, mainly identified by RT-PCR (reverse-transcriptase- coupled polymerase chain reaction) as VEGF121 and VEGF165 and to a lesser e xtent VEGF189, was comparable in tumor and control tissues. VEGF-B mBNA lev els were unchanged during the neoplastic progression of colonic mucosa. In contrast to KDR and FLT-4, the expression of VEGF-C and FLT-I genes increas ed in some pathological tissues. These results provide evidence that the ea rly and sustained increase in VEGF transcripts and the expression of multip le angiogenic factors and receptors contribute to the development of colon cancer, and thus constitute a putative target for antiangiogenic drug thera py. Int. J. Cancer 86:174-181, 2000. (C) 2000 Wiley-Liss, Inc.