Early diagnosis of pancreatic adenocarcinoma: role of stroma, surface proteases, and glucose-homeostatic agents.
OBJECTIVE
New-onset diabetes in pancreatic adenocarcinoma is due to a combination of insulin resistance and decreased β-cell function. Its differentiation from the common type 2 diabetes is the prerequisite for early diagnosis of pancreatic adenocarcinoma. Little attention has been paid to pancreatic stroma and surface proteases.


METHODS
The activated fibroblasts selectively express fibroblast activation protein α, a structural homolog of the ubiquitously expressed dipeptidyl peptidase 4. Their role in pancreatic carcinogenesis is reviewed.


RESULTS
Homodimers and heterodimers of both enzymes display high specificity for peptides and proteins with penultimate proline or alanine. Most glucose-homeostatic agents are candidate substrates of these enzymes. The biological activity of truncated substrates is decreased or absent.


CONCLUSIONS
The interactions of surface proteases with glucose-homeostatic agents may adequately explain the evolution of diabetes associated with pancreatic adenocarcinoma and differentiate it from the common type 2 diabetes.
Department of Medicine, First Faculty of Medicine and Central Military Hospital, Charles University, Prague, Czech Republic. premysl.fric@uvn.cz
Premysl
P
Fric
Miroslav
M
Zavoral
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D042241:Early Diagnosis; D010450:Endopeptidases; D018093:Gelatinases / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
D018819:Dipeptidyl Peptidase 4; D010450:Endopeptidases; D018093:Gelatinases; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C042807:DPP4 protein, human