Eva Hofsli1. 1. Institutt for fysiologi og biomedisinsk teknikk Det medisinske fakultet Norges teknisk-naturvitenskapelige universitet Medisinsk Teknisk Forskningssenter 7489 Trondheim. eva.hofsli@medisin.ntnu.no
Abstract
BACKGROUND: The peptide hormone somatostatin (SST) inhibits secretion from a wide variety of both endocrine and exocrine cells. It functions as a neurotransmitter and plays an important role in regulation of cell proliferation and differentiation. SST exerts its effects through binding to specific surface membrane receptors. MATERIAL AND METHODS: The article presents a literature-based review of the somatostatin receptor (SSTR) family, and diagnostic and therapeutic strategies based upon SSTR expression in neuroendocrine (NE) gastroenteropancreatic (GEP) tumours. RESULTS: Five different human SSTR subtypes have been characterised (SSTR1-5), and their genes cloned. The receptors are G-protein coupled, and binding activates several different signal mechanisms. SSTRs have a characteristic expression pattern both in the central nervous system and in peripheral organs. Many tumour cell lines as well as the majority of human tumours express SSTR mRNAs, usually more than one subtype. The frequency of expression is especially high in NE GEP tumours. SSTR scintigraphy has become an important diagnostic tool for staging of NE GEP tumours and it may also predict sensitivity to treatment with somatostatin analogues. These are regarded as the main choice for symptomatic treatment of hormone related syndromes related to NE GEP tumours. In contrast, the antitumour effects of somatostatin analogues in patients have been rather disappointing. More encouragingly, radiotherapy with radiolabeled somatostatin analogues has more recently been carried out with survival benefit. Gene therapy has shown promising results in animal studies. INTERPRETATION: Increased molecular understanding of the SSTR family and especially how the receptors are being regulated will probably lead to the development of new diagnostic and therapeutic strategies against cancer.
BACKGROUND: The peptide hormone somatostatin (SST) inhibits secretion from a wide variety of both endocrine and exocrine cells. It functions as a neurotransmitter and plays an important role in regulation of cell proliferation and differentiation. SST exerts its effects through binding to specific surface membrane receptors. MATERIAL AND METHODS: The article presents a literature-based review of the somatostatin receptor (SSTR) family, and diagnostic and therapeutic strategies based upon SSTR expression in neuroendocrine (NE) gastroenteropancreatic (GEP) tumours. RESULTS: Five different human SSTR subtypes have been characterised (SSTR1-5), and their genes cloned. The receptors are G-protein coupled, and binding activates several different signal mechanisms. SSTRs have a characteristic expression pattern both in the central nervous system and in peripheral organs. Many tumour cell lines as well as the majority of humantumours express SSTR mRNAs, usually more than one subtype. The frequency of expression is especially high in NE GEP tumours. SSTR scintigraphy has become an important diagnostic tool for staging of NE GEP tumours and it may also predict sensitivity to treatment with somatostatin analogues. These are regarded as the main choice for symptomatic treatment of hormone related syndromes related to NE GEP tumours. In contrast, the antitumour effects of somatostatin analogues in patients have been rather disappointing. More encouragingly, radiotherapy with radiolabeled somatostatin analogues has more recently been carried out with survival benefit. Gene therapy has shown promising results in animal studies. INTERPRETATION: Increased molecular understanding of the SSTR family and especially how the receptors are being regulated will probably lead to the development of new diagnostic and therapeutic strategies against cancer.