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Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy
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Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human

D C Danila1, J N Haidar, X Zhang

  • 1Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts 02114, USA.

The Journal of Clinical Endocrinology and Metabolism
|July 10, 2001
PubMed

Insights

Somatostatin analogs show antiproliferative effects in human pituitary tumors, independent of growth hormone secretion inhibition. Receptor expression did not predict treatment response, suggesting novel mechanisms for somatostatin therapy.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Somatostatin (SST) inhibits hormone secretion and cell proliferation via G protein-coupled receptors (GPCRs).
  • SST receptor subtypes (SSTR) 1, 2, 3, and 5 are expressed in human pituitary somatotroph cells.
  • The effects of SST analogs on pituitary tumor proliferation and the predictive value of SSTR expression remain unclear.

Purpose of the Study:

  • To investigate the effects of SST-14, lanreotide, and SSTR 2/5-specific analogs on proliferation and GH secretion in human somatotroph adenomas.
  • To determine if SSTR expression predicts the antiproliferative effects of SST analogs.
  • To explore the relationship between SST analog effects on GH secretion and tumor cell proliferation.

Main Methods:

  • Primary culture of 18 human somatotroph pituitary adenomas.
  • Treatment with SST-14, lanreotide, SSTR 2-specific analog (BIM-23190), and SSTR 5-specific analog (BIM-23268).
  • Assessment of cell proliferation and growth hormone (GH) secretion inhibition; SSTR mRNA expression analysis.

Main Results:

  • SST-14, lanreotide, BIM-23190, and BIM-23268 significantly inhibited cell proliferation in a subset of tumors (median 16% suppression).
  • GH secretion was inhibited by SST-14, lanreotide, BIM-23190, and BIM-23268 (median 33% inhibition).
  • A dissociation was observed between antiproliferative effects and GH secretion inhibition; SSTR 2/5 expression did not predict response.

Conclusions:

  • Somatostatin analogs can inhibit proliferation of human somatotroph tumors independently of their effects on GH secretion.
  • SSTR 2 and 5 expression does not predict antiproliferative efficacy, suggesting complex regulatory mechanisms.
  • Further research is needed to elucidate the precise mechanisms underlying SST-induced antiproliferative effects in pituitary tumors.

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