Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin αV and integrin β3 in human neuroendocrine tumors

Abstract

Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin αv, and integrin β3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (p<0.001) and normal liver tissue (p<0.01). For integrin β3 there was also a borderline significant lower level of mRNA in neuroendocrine tumors compared to both colorectal liver metastases (p=0.10) and normal liver tissue (p=0.06). In neuroendocrine tumors, gene-expression was highly variable of VEGF (530-fold), integrin v (23-fold) and integrin β3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF and integrin β 3 were lower in neuroendocrine tumors than in colorectal liver metastases and were highly variable. Therefore, individual selection of patients may be necessary if anti-angiogenesis treatment is to be successful in patients with neuroendocrine tumors.