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Human pancreatic cancer cell lines do not express receptors for somatostatin
J Gillespie1, G J Poston, M Schachter
1Academic Surgical Unit, Imperial College of Science, Technology & Medicine, St. Mary's Hospital Medical School, London, UK.
Abstract:
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.
Insights
Somatostatin (SS) and its analogues did not inhibit human pancreatic cancer cell growth in vitro. This lack of efficacy is due to the absence of somatostatin receptors on these cancer cells, questioning their therapeutic use.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Somatostatin (SS) and its analogues show promise in suppressing pancreatic cancer growth in animal models.
- Epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) are known stimulators of pancreatic cancer cell proliferation.
Purpose of the Study:
- To investigate the in vitro effects of SS-14 and its analogue RC-160 on human pancreatic cancer cell lines (MiaPaCa-2, Panc-1).
- To determine if SS-14 and RC-160 can inhibit EGF- or IGF-1-stimulated pancreatic cancer cell growth.
- To explore the presence of somatostatin receptors on human pancreatic cancer cell lines.
Main Methods:
- In vitro cell culture of human pancreatic cancer cell lines MiaPaCa-2 and Panc-1.
- Treatment with somatostatin (SS)-14 and its analogue RC-160, with or without EGF/IGF-1 stimulation.
- Growth inhibition assays.
- Binding studies using radiolabeled somatostatin (125I-Tyr11 somatostatin) to assess receptor presence and affinity (Kd, Bmax) on AR42J (rat pancreatic cancer cell line) and human cell lines.
Main Results:
- Neither SS-14 nor RC-160 inhibited the in vitro growth of human pancreatic cancer cell lines MiaPaCa-2 and Panc-1.
- RC-160 demonstrated inhibition of epidermal growth factor (EGF)-stimulated growth in a rat pancreatic cancer cell line (AR42J).
- High-affinity somatostatin binding sites were detected on AR42J cells, but not on MiaPaCa-2 or Panc-1 cells.
Conclusions:
- The absence of somatostatin receptors on human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 explains the lack of growth inhibition by SS-14 and RC-160 in vitro.
- These findings suggest that somatostatin and its analogues may not be effective as monotherapy for human pancreatic cancer.
- Further research is needed to evaluate combination therapies or alternative treatment strategies for pancreatic cancer.