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• VEGF expression by stage

VEGF expression in colorectal cancer by stage

Relative levels of VEGF-type expression by stage⁹

Hanrahan et al investigated the expression of 4 members of the VEGF family of ligands in normal tissue and at different stages of colorectal cancer. Of these 4 ligands, VEGF-A (commonly known as VEGF) was the most commonly expressed in malignant tissue, and was expressed from the adenoma stage through the Dukes' C stage. This image shows the relative expression levels of each VEGF ligand during various stages of colorectal cancer.⁹

Adapted from Hanrahan 2003. Reproduced with permission from the Journal of Pathology.

Preclinical models confirm the important role of vascular endothelial growth factor (VEGF) and angiogenesis in the progression of colorectal cancer. In colon cancer cell lines, Kondo and colleagues found that VEGF-expressing tumors had more vascularity and more metastatic potential (both hepatic metastasis and peritoneal dissemination) than control tumors in which VEGF was not upregulated. These results suggest that VEGF stimulates angiogenesis in colon cancer and accelerates cell growth in metastatic sites.¹⁰

All variants of the VEGF ligand are expressed in colon cancer, with VEGF-A (commonly referred to as VEGF) predominating. Hanrahan and colleagues demonstrated this in a study measuring the gene expression of various VEGF ligands and receptors in colorectal cancer. The investigators observed that VEGF-A mRNA (which corresponds to VEGF ligand production) was the most commonly expressed of the VEGF ligands. Their work also showed that the amount of each variant of the VEGF family expressed by the tumor differed by tumor stage. Specifically, VEGF-A and VEGF-B were more abundant in adenomas compared with normal tissue, and that VEGF-A and VEGF-C were more common in carcinomas compared with normal tissues.⁹

The findings of Kondo et al and Hanrahan et al suggest that the "angiogenic switch" is activated early in the course of cancer progression and that VEGF is associated with initiation and maintenance of angiogenesis in colon cancer.^9,10

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