Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin.
OBJECTIVE
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 beta cells (BRIN-BD11). The factor responsible was characterized by exposing beta 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 approximately 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.
Ding
X
X
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska, USA.
Flatt
P R
PR
Permert
J
J
Adrian
T E
TE
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D000682:Amyloid; D058228:Islet Amyloid Polypeptide