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

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


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.

Publication types

  • Comparative Study

MeSH terms

  • Adenomatous Polyps / metabolism*
  • Adenomatous Polyps / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • DNA Primers / chemistry
  • Disease Progression
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoenzyme Techniques
  • RNA, Messenger / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D


  • DNA Primers
  • Endothelial Growth Factors
  • RNA, Messenger
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor