Putative pancreatic cancer-associated diabetogenic factor: 2030 MW peptide.
BACKGROUND
Pancreatic adenocarcinoma causes diabetes mellitus by releasing factors interfering with glucose metabolism.


OBJECTIVE
We verified in isolated rat hepatocytes the molecular weight (MW) of the fraction from pancreatic cancer cell conditioned media (CM) that altered glucose metabolism and ascertained, using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis, whether there is any common peptide in CM and in the sera of patients with pancreatic cancer.


METHODS
Sera was obtained from patients with pancreatic cancer ( n = 14) and chronic pancreatitis ( n = 9) and healthy control subjects ( n = 10). Conditioned medium (CM) was obtained from the following cell lines: MIA PaCa 2, PSK-1, PANC-1, and CAPAN-1. Two fractions (MW of less than 30,000 Da and less than 10,000 Da) were obtained from patients' sera, from CM, and from non-CM (NCM) after two-step ultrafiltration. Rat hepatocytes were incubated with CM and NCM. The peptide profile of patients' sera, CM, and NCM were analyzed using MALDI-MS.


RESULTS
In rat hepatocytes, glucose metabolism was impaired by CM from all the pancreatic cancer cell lines and by CM with an MW of less than 10,000 Da. Two peptides (m/z 2030 and 2726) were found in CM and patients' sera. Only the peptide at m/z 2030 was found to be associated with the presence of diabetes.


CONCLUSIONS
A peptide at m/z 2030 may be a putative pancreatic cancer-associated diabetogenic factor.
Basso
Daniela
D
Department of Laboratory Medicine, University of Padova, Italy.
Valerio
Anna
A
Seraglia
Roberta
R
Mazza
Saverio
S
Piva
Maria Grazia
MG
Greco
Eliana
E
Fogar
Paola
P
Gallo
Nicoletta
N
Pedrazzoli
Sergio
S
Tiengo
Antonio
A
Plebani
Mario
M
D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism*; D010195:Pancreatitis / Q000097:blood; D010907:Pituitary Hormones / Q000302:isolation & purification*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; C488867:DGF protein, rat; D010907:Pituitary Hormones; C010912:diabetogenic factor, human; D019344:Lactic Acid; D005947:Glucose