G protein–coupled receptor signaling in human ductal pancreatic cancer cells: Neurotensin responsiveness and mitogenic stimulation
✍ Scribed by Nova M. Ryder; Sushovan Guha; Oscar J. Hines; Howard A. Reber; Enrique Rozengurt
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 363 KB
- Volume
- 186
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Neuropeptides and their corresponding G protein±coupled receptors (GPCRs) are increasingly implicated in the autocrine/paracrine stimulation of growth of human cancers. We report that neurotensin induced rapid Ca 2 mobilization from intracellular stores followed by Ca 2 in¯ux in ®ve human ductal pancreatic cancer cell lines: HPAF-II, Capan-1, Capan-2, PANC-1, and MIA PaCa-2. In addition, most cell lines exhibited Ca 2 responses to multiple neuropeptides including bombesin, bradykinin, cholecystokinin, and vasopressin and to bioactive lipids, including lysophosphatidic acid (LPA), that also act via GPCRs. The well-differentiated line HPAF-II responded to at least seven independent GPCR agonists. The concentrations of neurotensin required to induce halfmaximal effects (EC 50 ) in HPAF-II and PANC-1 cells were 5 and 8 nM, respectively. Digital ¯uorescence image analysis to measure Ca 2 responses in single cells revealed that 90% or more of HPAF-II and PANC-1 cells responded to 10 nM neurotensin. Addition of neurotensin to PANC-1 cells also induced rapid and dose-dependent extracellular-regulated protein kinase (ERK-1 and ERK-2) activation and subsequently, stimulated DNA synthesis. The signaling complexity of GPCRs uncovered by these studies reveals a new aspect in the biology of human pancreatic cancer and could offer the basis for new approaches to the treatment of this disease.