Human pancreatic cancer cell lines do not express receptors for somatostatin.
The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with 125I-Tyr11 somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 +/- 0.05 nM and a Bmax of 2.1 +/- 0.26 pmoles mg-1 protein on AR42J but not displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer.
Gillespie
J
J
Academic Surgical Unit, Imperial College of Science, Technology & Medicine, St. Mary's Hospital Medical School, London, UK.
Poston
G J
GJ
Schachter
M
M
Guillou
P J
PJ
D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; C051458:vapreotide; D013004:Somatostatin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I