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

We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEG F-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carc inoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA ex pression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenom atous polyps. Immuohistochemistry and ELISA assessed protein expression. VE GF-D mRNA expression was significantly lower in both polyps and CRCs compar ed with normal mucosa (P=.0002 and .002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and .004, respectively), b ut not polyps (P=.22 and P=.5, respectively). Receptor expression was simil ar in tumor tissue and normal mucosae. Tumors with lymph node metastases ha d 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 re ceptors, and produce the angiogenic switch required for tumor growth. Incre ased expression of VEGF-A within CRCs was associated with lymphatic metasta ses, and therefore, this member of the VEGF family may be the most importan t in determining metastatic spread.