Early Diagnosis of Pancreatic Adenocarcinoma Role of Stroma, Surface Proteases, and Glucose-Homeostatic Agents
Abstract
Objectives: New-onset diabetes in pancreatic adenocarcinoma is due to a combination of insulin resistance and decreased A-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 alpha , 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.