Pancreatic cancer cells selectively stimulate islet β cells to secrete amylin

X. Ding, P. R. Flatt, J. Permert, T. E. Adrian

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

Background and Aims: Patients with pancreatic adenocarcinoma have a high incidence of diabetes, profound insulin resistance, and high circulating amylin concentrations. It was hypothesized that pancreatic cancer cells produce a factor that stimulates islets to secrete amylin but not insulin. Methods: Amylin and insulin secretion were measured after coculture of pancreatic cancer cells with β cells (BRIN-BD11). The factor responsible was characterized by exposing β cells to cancer cell-conditioned medium. Results: Coculture with pancreatic (PANC-1 HPAF, and MiaPaCa2) but not colonic cancer cells (Colo 320) significantly increased amylin secretion but did not change insulin output. This effect was both time and cell number dependent. Coculture with PANC-1 or HPAF cells significantly decreased intracellular amylin, but not insulin, content. PANC-1 or HPAF cell- conditioned medium also increased amylin secretion and decreased intracellular amylin content. The factor responsible was extracted under both neutral and acidic conditions, was heat labile, and had a molecular weight of ~1500. Conclusions: A soluble factor from pancreatic cancer cells selectively stimulates amylin secretion from islet cells, explaining the excessive amylin secretion found in pancreatic cancer. Because elevation of amylin concentration 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.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalGastroenterology
Volume114
Issue number1
DOIs
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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