Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors.
Type-II diabetes is a risk factor for pancreatic cancer. In addition, diabetic patients present with more advanced tumors and have shortened survival compared to stage-matched counterparts. We hypothesize that the diabetic endocrine milieu, particularly elevated plasma insulin, favors pancreatic cancer growth. This study examines six human pancreatic cancer cell lines for the presence of insulin receptors and the influence of insulin on tumor proliferation. Classical competitive binding assays are performed using [125I insulin. Cell proliferation assays are conducted over 3 days on cultured cell lines (n = 6 replicates) with increasing concentrations of insulin. Insulin receptors are demonstrated on all six cell lines and dose dependent increases in cell proliferation (15-120% of control) are demonstrated in response to insulin. Patients with type-II diabetes hypersecrete insulin. The presence of high-affinity insulin receptors and dose dependent increases in pancreatic cancer cell proliferation with insulin supports the hypothesis that insulin may be an important tumor growth promoter in diabetes, particularly if paracrine mechanisms are involved. Additional study is required to determine whether other islet peptides altered in diabetes influence tumor growth and whether elevated plasma insulin favors pancreatic cancer induction.
Fisher
W E
WE
Department of Surgery, Ohio State University, Columbus 43210, USA.
Boros
L G
LG
Schirmer
W J
WJ
D000230:Adenocarcinoma; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism*; D012307:Risk Factors; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007328:Insulin; D011972:Receptor, Insulin