VEGF-B expression in colorectal carcinomas and its relevance for tumor progression.

The biological behavior of VEGF-B, a ligand of the receptor VEGFR-1, is still enigmatic. Despite its high sequence homology to the better known angiogenetic factor VEGF-A, the function of VEGF-B has remained elusive. Especially, its role in tumor biology has thus far not been defined. In the present study we address the question of whether VEGF-B could play a role in the metastatic process of colorectal carcinomas (CRC). Using immunohistochemistry we investigated its expression in the tumor tissue of 91 non-metastatic, lymphogenous-metastatic and haematogenous-metastastic CRC. Independently of metastatic status, VEGF-B was expressed in endothelial as well as in tumor cells. 81% of the CRC showed a positive, partly focal, partly disseminated endothelial expression in intratumoral vessels and the vascular fraction throughout the invasive tumor margin. Almost all of the VEGF-B positive vessels were of blood vascular origin. Many of these were thick-walled blood vessels with atherosclerotic changes characterizing preexistent but not angiogenetic vasculature. Thus it appears that VEGF-B might be an important ligand to ensure the blood supply for tumor survival. 46% of the CRC presented an additional tumoral VEGF-B expression which significantly correlated with haematogenous metastasis (p=0.006). These morphological results provide evidence for a probable pathobiological significance of VEGF-B in the tumor progression of CRC, especially in the case of haematogenous metastasis. It appears that VEGF-B might be an important ligand in the signalling between the tumor and preexisting blood vessels to ensure a functional blood supply for tumor survival.