Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth.
The hormone obestatin, which is derived from the same precursor as ghrelin and whose receptor(s) is still unrecognized, possesses a variety of metabolic/modulatory functions mostly related to food intake suppression and reduction of gastrointestinal motility. The distribution of obestatin in normal and neoplastic human tissues is poorly understood. We report that in fetal tissue samples, obestatin peptide was detected in the thyroid, pituitary, lung, pancreas and gastrointestinal tract, usually being co-localized with chromogranin A. In adult tissues, obestatin protein expression was restricted to pituitary, lung, pancreas and gastrointestinal tract and was co-localized strictly with ghrelin. By contrast, in endocrine tumours obestatin was expressed in a small fraction of thyroid, parathyroid, gastrointestinal and pancreatic neoplasms, in most cases with a focal immunoreactivity and co-localized with ghrelin. Messenger RNA levels of the specific fragments of ghrelin and obestatin were comparable in both normal and tumour samples, confirming that post-translational mechanisms rather than alternative splicing events lead to ghrelin/obestatin production. Finally, in TT and BON-1 cell lines obestatin induced antiproliferative effects at pharmacological doses, opposite to those observed with ghrelin. In summary, our data demonstrate that obestatin is produced by the same endocrine cells that express ghrelin in normal tissues from fetal to adult life, whereas, as compared to ghrelin, in neoplastic conditions it is down-regulated by post-translational modulation and shows potential antiproliferative properties in vitro.
Volante
Marco
M
Department of Clinical and Biological Sciences at San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
Rosas
Rosj
R
Ceppi
Paolo
P
Rapa
Ida
I
Cassoni
Paola
P
Wiedenmann
Bertram
B
Settanni
Fabio
F
Granata
Riccarda
R
Papotti
Mauro
M
D037881:Aborted Fetus / Q000737:chemistry; D000328:Adult; D000704:Analysis of Variance; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015342:DNA Probes / Q000235:genetics; D005455:Fluorescent Antibody Technique; D054439:Ghrelin / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D055099:Neuroendocrine Cells / Q000737:chemistry*; D018358:Neuroendocrine Tumors / Q000737:chemistry*; D009490:Neurosecretory Systems / Q000737:chemistry / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014018:Tissue Distribution
D000906:Antibodies; D015342:DNA Probes; D054439:Ghrelin