THE PANCREATIC-CANCER CELL-LINE MIA PACA2 PRODUCES ONE OR MORE FACTORS ABLE TO INDUCE HYPERGLYCEMIA IN SCID MICE

A reduced glucose tolerance or frank diabetes mellitus is a frequent f inding in patients with pancreatic cancer. The aim of this study was t o verify whether the pancreatic cancer cell line MIA PaCa2 was able to produce any factor which could induce hyperglycemia in SCID (severe c omplete immunodeficient) mice. MIA PaCa2 cells were cultured in Dulbec co's modified Eagle's medium (DMEM) for 7 days. Twenty-five female SCI D mice were used. They were daily i.p. injected with 300 ul of cell cu lture supernatants (Group T, n=13) or with 300 ul of DMEM (Group C, n= 12) and followed up for 82 days. Blood glucose levels were significant ly higher in Group T than in Group C on days 10 and 25. Intravenous gl ucose tolerance test, success-fully performed in 9 animals (4 controls and 5 treated), demonstrated a significantly reduced glucose toleranc e in Group T compared to Group C mice. At sacrifice, plasma and pancre atic insulin and glucagon levels did not vary between groups. The rati o between pancreatic and plasma insulin was significantly lower in Gro up T than in Group C. We conclude that: 1. The pancreatic cancer cell line MIA PaCa2 produces one or more soluble factors able to cause hype rglycemia in vivo; 2. this effect is not immunologically mediated, and 3. this/these factor/s could both interfere with the pancreatic beta cells and/or with insulin peripheral action.