Membrane receptors for peptides in experimental and human pancreatic cancers

Matyas Fekete, Attila Zalatnai, Ana Maria Comaru-Schally, Andrew Victor Schally

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Membrane receptors for [D-Trp6]-luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH), somatostatin (SS-14), and epidermal growth factor (EGF) were investigated in experimental N-nitrosobis-(2-oxopropyl)-amine (BOP)-induced pancreatic cancers of hamsters and in specimens of normal human pancreas and human pancreatic cancer obtained from autopsies. Membrane receptors for [D-Trp6]-LH-RH were absent in the pancreas of normal hamsters, but appeared after the carcinoma was induced with BOP. Binding capacity of SS-14 receptors was lower in membranes of BOP-induced pancreatic cancers than in the normal pancreas. In the BOP-induced pancreatic cancers, the receptors were also characterized following in vivo treatment of hamsters with microcapsules of the agonist [D-Trp6]-LH-RH, somatostatin analog RC-160, and the combination of both peptides, which resulted in significant tumor inhibition. Therapy with [D-Trp6]-LH-RH and RC-160, alone or in combination, decreased the binding capacity of receptors for [D-Trp6]-LH-RH, but increased B(max) for SS-14. There were no significant changes in characteristics of the EGF receptor following these therapies. Membranes from human pancreatic cancers showed binding sites for [D-Trp6]-LH-RH, but no binding was detected in normal human pancreas. The presence of receptors for LH-RH in pancreatic tumors of hamster and humans raises the intriguing possibility that LH-RH could be involved in complex interactions that contribute to the appearance of pancreatic cancer. The binding capacity of receptors for SS-14 in human pancreatic cancer membranes was lower, while B(max) for EGF was higher, as compared to normal pancreas. Observed changes in receptors and tumor suppression suggest that the agonist ]D-Trp6]-LH-RH and somatostatin analogs might exert some direct inhibitory effects on experimental pancreatic cancer of hamsters. It is possible that LH-RH agonists and somatostatin analogs could also be used for treatment of human pancreatic cancer. The presence of membrane receptors for [D-Trp6]-LH-RH, SS-14, and EGF in specimens of human pancreatic cancer also implies that this malignancy might be responsive to hormonal manipulations.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalPancreas
Volume4
Issue number5
DOIs
StatePublished - Oct 1989
Externally publishedYes

Keywords

  • Binding sites for luteinizing hormone-releasing hormone (LH-RH)
  • Epidermal growth factor
  • Hormonal manipulations
  • Pancreatic carcinoma
  • Somatostatin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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