title: Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 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 alphaV, and integrin beta3, 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 beta3 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 alphaV (23-fold) and integrin beta3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF and integrin beta3 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.
authors.affiliation: Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark. joxboll@mfi.ku.dk
authors.forename: Jytte
authors.initials: J
authors.lastname: Oxboel
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.forename: Ulrich
authors.initials: U
authors.lastname: Knigge
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000556:secondary; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D039564:Integrin alphaV / Q000096:biosynthesis* / Q000235:genetics; D039661:Integrin beta3 / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D039564:Integrin alphaV; D039661:Integrin beta3; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A