Promoter Hypermethylation-Related Reduced Somatostatin Production Promotes Uncontrolled Cell Proliferation in Colorectal Cancer.

BACKGROUND: Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line. METHODS: Colonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined using methylation-sensitive restriction enzyme digestion. RESULTS: In case of normal aging SST mRNA expression did not alter, but decreased in cancer (p<0.05). The ratio of SST immunoreactive cells was significantly higher in children (0.70%+/-0.79%) compared to CRC (0%+/-0%) (p<0.05). Octreotide significantly increased the proportion of apoptotic Caco-2 cells. SST showed significantly higher methylation level in tumor samples (30.2%+/-11.6%) compared to healthy young individuals (3.5%+/-1.9%) (p<0.05). CONCLUSIONS: In cancerous colonic mucosa the reduced SST production may contribute to the uncontrolled cell proliferation. Our observation that in colon cancer cells octreotide significantly enhanced cell death and attenuated cell proliferation suggests that SST may act as a regulator of epithelial cell kinetics. The inhibition of SST expression in CRC can be epigenetically regulated by promoter hypermethylation

Radiopeptides from diagnosis to therapy

Radiopeptides are playing an increasing role in the diagnosis of disease. Initially based on the somatatostatin system, early research concentrated on identifying tumours of neuroendocrine origin. New techniques with artificial peptides are extending their role into other areas such as thrombus formation and heart disease. It has been shown that radiopeptides have excellent labelling new methods have looked at therapy starting with high activities of In-111 pentetreotide to the development of Y-90 based products and new and novel peptides and radio isotopes. Outside of PET there are the most exciting developments in nuclear medicine.<br>Radiopeptídeos estão desempenhando um papel cada vez mais relevante no diagnóstico de doenças. Inicialmente dedicado ao sistema somatostatinérgico, a pesquisa nesta área concentrava-se em identificar tumores de origem neuroendócrina. Novas técnicas com peptídeos artificiais estão estendendo seu papel em outras áreas, tais como a formação de trombos em doenças cardíacas. Tem sido mostrado novos e excelentes métodos de marcação de radiopeptídeos começando por aqueles com alta atividade, tais como In-111 pentetreotídeo, ao desenvolvimento de produtos com Y-90 e recentes peptídeos e radioisótopos. Além do PET, há interessantes desenvolvimentos em Medicina Nuclear