PANCREATIC-CANCER CELLS SELECTIVELY STIMULATE ISLET BETA-CELLS TO SECRETE AMYLIN

Background & Aims: Patients with pancreatic adenacarcinoma have a high incidence of diabetes, profound insulin resistance, and high circulat ing amylin concentrations. It was hypothesized that pancreatic cancer cells produce a factor that stimulates islets to secrete amylin but no t insulin, Methods: Amylin and insulin secretion were measured after c oculture of pancreatic cancer cells with beta cells (BRIN-BD11). The f actor responsible was characterized by exposing beta cells to cancer c ell-conditioned medium. Results: Coculture with pancreatic (PANG-1 HPA F, and MiaPaCa2) but not colonic cancer cells (Colo 320) significantly increased amylin secretion but did not change insulin output, This ef fect was both time and cell number dependent, Coculture with PANG-1 or HPAF cells significantly decreased intracellular amylin, but not insu lin, content, PANG-1 or HPAF cell-conditioned medium also increased am ylin secretion and decreased intracellular amylin content. The factor responsible was extracted under both neutral and acidic conditions, wa s heat labile, and had a molecular weight of similar to 1500. Conclusi ons: A soluble factor from pancreatic cancer cells selectively stimula tes amylin secretion from islet cells, explaining the excessive amylin secretion found in pancreatic cancer, Because elevation of amylin con centration is an early feature of pancreatic cancer, characterization and measurement of the tumor-derived amylin-releasing factor might be valuable in the early detection of this disease.