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

Abstract

Because the crucial role of angiogenesis has been demonstrated in tumor growth and metastasis, the present study was undertaken to characterize the relative expression of vascular endothelial growth factors VEGF (vascular endothelial growth factor), VEGF‐B, VEGF‐C, and their receptors KDR (kinase insert 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 quantified by Northern blot in 72 tumor samples matched with control tissues. VEGF gene expression was 1.4 times higher in adenocarcinomas than in control tissues (p = 0.02), but did not increase further between Astler‐Coller tumor stages A and D, and did not correlate with disease recurrence for patients at stages B2 or C. In adenomas, VEGF mRNA levels were not significantly different from those in the paired control colonic mucosa. The expression pattern of VEGF isoforms, mainly identified by RT‐PCR (reverse‐transcriptase‐coupled polymerase chain reaction) as VEGF121 and VEGF165 and to a lesser extent VEGF189, was comparable in tumor and control tissues. VEGF‐B mRNA levels were unchanged during the neoplastic progression of colonic mucosa. In contrast to KDR and FLT‐4, the expression of VEGF‐C and FLT‐1 genes increased in some pathological tissues. These results provide evidence that the early and sustained increase in VEGF transcripts and the expression of multiple angiogenic factors and receptors contribute to the development of colon cancer, and thus constitute a putative target for anti‐angiogenic drug therapy. Int. J. Cancer 86:174–181, 2000. © 2000 Wiley‐Liss, Inc.

Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role of the Rho–Rho kinase axis and tumor microenvironment

“…Hypoxic environment has been shown to play a major role in tumor angiogenesis, cancer growth, and metastasis. The hypoxia-dependent angiogenic switch in human solid tumors is an early event linked to the secretion of high levels of VEGF and several angiogenic factors by cancer cells, as well as by endothelial cells or other cell types in the tumor stroma (Andre et al, 2000). The NO/cGMP/ PKG and calcium-dependent signaling pathways are also involved in the regulation of tumor cell invasiveness and angiogenesis linked to endothelial cell proliferation, morphogenesis, and tumor invasion (Kawasaki et al, 2003).…”

The importance of −460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer

“…Quantitative analysis of VEGF-A in CRC tissue and normal colonic and rectal tissue has been performed in several studies, and high levels of tumour VEGF-A have been correlated with poor prognosis (Andre et al 2000;George et al 2001;Broll et al 2001;Ferroni et al 2005;Kuramochi et al 2006;Altomare et al 2007). In general, VEGF-A seems to be up-regulated in CRC compared to normal tissue at both mRNA and protein level, but the possible relationship with SNPs needs further investigation.…”

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

“…However, most studies showed that VEGF expression at the tissue level is not a good predictor of prognosis. 8,12,13 Placenta growth factor (PlGF), a dimeric glycoprotein with 53% homology to VEGF, 14,15 which binds to VEGF receptor-1 (Flt-1), but not to VEGF receptor-2 (Flk-1), may function by modulating VEGF activity. 16 Flt-1 exists in two forms due to alternative splicing: the full-length receptor, which transmits angiogenic signals, and a soluble secreted form of Flt-1 (sFlt-1), which lacks the transmenbrane and cytoplasmic domains but retains the ability to bind to its ligands.…”