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Comparative Study
. 2001 Sep-Oct;3(5):420-7.
doi: 10.1038/sj.neo.7900186.

VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression

M L George  1 , M G Tutton, F Janssen, A Arnaout, A M Abulafi, S A Eccles, R I Swift
Affiliations
Comparative Study

VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression

M L George et al. Neoplasia. 2001 Sep-Oct.

Abstract

We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immunohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and.002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and.004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.

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Figures

Figure 1
Figure 1
(A) Comparison of corrected VEGF-D protein ratios in colorectal cancers and paired normal mucosa (horizontal bar represents median). (B) Correlation of corrected VEGF-D protein ratios with RT-PCR products (r= 0.36, P=.03).
Figure 2
Figure 2
VEGF-D RT-PCR products of five paired tumors (T) and paired normal mucosa (N).
Figure 3
Figure 3
mRNA expression of VEGF-A, VEGF-C, and VEGF-D through the adenoma-carcinoma sequence. Median values with interquartile range (box) and range (whiskers).
Figure 4
Figure 4
Scatter plot of mRNA expression in normal mucosa, node-negative, and node-positive tumors (horizontal bar represents median).
Figure 5
Figure 5
(A–D) Immunostaining of tumor cytoplasm with VEGF-A (A), VEGF-C (B), VEGF-D (C), and tumour endothelial cells with VEGFR-3 (indicated by black arrow) (D).
See this image and copyright information in PMC

References

    1. Folkman J. What is the evidence that tumors are angiogenesis-dependent? J Natl Cancer Inst. 1990;82:4–6. - PubMed
    1. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–364. - PubMed
    1. Wei MH, Popescu NC, Lerman MI, Merrill MJ, Zimonjic DB. Localization of the human vascular endothelial growth factor gene, VEGF, at chromosome 6p12. Hum Genet. 1996;97:794–797. - PubMed
    1. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–1039. - PMC - PubMed
    1. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem. 1992;267:26031–26037. - PubMed

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