Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?
BACKGROUND
Our aim was to identify the pancreatic cancer diabetogenic peptide.


METHODS
Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE.


RESULTS
A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation.


CONCLUSIONS
The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus.
Basso
Daniela
D
Department of Laboratory Medicine, University of Padua, Via Giustiniani 2, 35128 Padova, Italy.
Greco
Eliana
E
Fogar
Paola
P
Pucci
Piero
P
Flagiello
Angela
A
Baldo
Goretta
G
Giunco
Silvia
S
Valerio
Anna
A
Navaglia
Filippo
F
Zambon
Carlo-Federico
CF
Falda
Alessandra
A
Pedrazzoli
Sergio
S
Plebani
Mario
M