Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation

Diego Ferone, Marica Arvigo, Claudia Semino, Philippe Jaquet, Alexandru Saveanu, John E. Taylor, Jacques Pierre Moreau, Michael D. Culler, Manuela Albertelli, Francesco Minuto, Antonina Barreca

Research output: Contribution to journalArticlepeer-review

Abstract

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst 2 and D 2R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst 2 and the long isoform of the D 2R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst 5 and to a lesser extent sst 3 and D 4R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [ 3H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P <0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number6
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Dopamine receptors
  • Growth factors
  • Lung carcinoma
  • Receptor dimerization
  • Somatostatin receptors

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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