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Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth

Marco Volante1, Rosj Rosas, Paolo Ceppi

  • 1Department of Clinical and Biological Sciences at San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.

The Journal of Pathology
|April 18, 2009
PubMed

Insights

Obestatin, a hormone co-produced with ghrelin, is found in various human tissues. While present in normal endocrine cells, obestatin expression decreases in tumors, potentially exhibiting antiproliferative effects.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Gastroenterology

Background:

  • Obestatin is a hormone derived from the same precursor as ghrelin.
  • Its receptors and functions, particularly in human tissues, are not fully understood.
  • Known functions include suppression of food intake and reduced gastrointestinal motility.

Purpose of the Study:

  • To investigate the distribution of obestatin peptide and protein in normal and neoplastic human tissues.
  • To compare obestatin and ghrelin expression patterns.
  • To explore the post-translational mechanisms of obestatin production and its antiproliferative effects.

Main Methods:

  • Immunohistochemistry to detect obestatin and ghrelin protein expression in fetal, adult, and tumor tissues.
  • Analysis of messenger RNA (mRNA) levels for ghrelin and obestatin fragments.
  • In vitro studies using TT and BON-1 cell lines to assess obestatin's antiproliferative effects.

Main Results:

  • Obestatin peptide was detected in fetal thyroid, pituitary, lung, pancreas, and gastrointestinal tract.
  • In adult tissues, obestatin co-localized strictly with ghrelin in the pituitary, lung, pancreas, and gastrointestinal tract.
  • Obestatin was expressed in a subset of endocrine tumors, often focally and co-localized with ghrelin; mRNA levels were comparable, suggesting post-translational regulation.
  • Obestatin demonstrated antiproliferative effects in TT and BON-1 cell lines at pharmacological doses.

Conclusions:

  • Obestatin is produced by the same endocrine cells as ghrelin throughout human development.
  • Neoplastic conditions lead to down-regulation of obestatin, likely via post-translational modulation.
  • Obestatin exhibits potential in vitro antiproliferative properties, contrasting with ghrelin's effects.

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