Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: Implications for pancreatic carcinogenesis Journal Article
| Authors: | Bhanot, U. K.; Möller, P. |
| Article Title: | Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: Implications for pancreatic carcinogenesis |
| Abstract: | The pathobiology of chronic pancreatitis (CP) remains enigmatic despite remarkable progress made recently in uncovering key mechanisms involved in the initiation and progression of the disease. CP is increasingly thought of as a multifactorial disorder. Apoptosis plays a role in parenchymal destruction, the pathological hallmark of CP. The apoptotic mechanisms preferentially target the exocrine compartment, leaving endocrine islets relatively intact for a prolonged period. Exocrine cells shed their immunoprivileged status, express death receptors, and are rendered susceptible to apoptosis induced by death ligands on infiltrating lymphocytes, and released locally by activated pancreatic stellate cells. Islet cells retain their immunoprivileged status and activate anti-apoptotic programs through NF-κB. Ductal changes, including distortion, dilatation, and pancreatic ductal hypertension in the setting of CP, induce genomic damage and increased cell turnover. In addition, signaling mechanisms that play a role in the development of embryonic pancreas are reinstated, thus, playing a role in repair, regeneration, and transformation. This, in turn, leads to acino-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Some of these pathways are activated in pancreatic cancer. We attempt to integrate the current knowledge and major concepts in the pathogenesis of CP and to explain the mechanism of differential cell loss. We also discuss the possible implications of signaling pathway activation in pancreatic inflammation, relevant to the cellular transformation that leads to pancreatic neoplasia.©2009 USCAP, Inc All rights reserved. |
| Keywords: | signal transduction; platelet derived growth factor; unclassified drug; review; nonhuman; pathophysiology; pancreas cancer; pancreatic neoplasms; pancreas; cd8+ t lymphocyte; metabolism; apoptosis; transforming growth factor beta; sonic hedgehog protein; hedgehog proteins; notch receptor; immunoglobulin enhancer binding protein; caspase 3; physiology; carcinogenesis; immunology; immune response; gamma interferon; cyclooxygenase 2; pancreatic carcinogenesis; pancreatitis; parenchymal injury; alcohol; angiotensin ii; cyclooxygenase 1; death receptor 4; death receptor 5; inhibitor of apoptosis protein; inhibitor of apoptosis protein 1; prostaglandin e2; serine protease inhibitor kazal type 1; serine proteinase inhibitor; transmembrane conductance regulator; trypsinogen; tumor necrosis factor related apoptosis inducing ligand; death receptor; ptgs2 protein, human; cell damage; chronic pancreatitis; cystic fibrosis; diabetes mellitus; exocrine cell; pancreas insufficiency; sentinel event; stellate cell; pancreas duct; pancreas tumor; inhibitor of apoptosis proteins; nf-kappa b; pancreatic ducts; pancreatitis, chronic; receptors, death domain; receptors, notch |
| Journal Title: | Laboratory Investigation |
| Volume: | 89 |
| Issue: | 5 |
| ISSN: | 0023-6837 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-05-01 |
| Start Page: | 489 |
| End Page: | 497 |
| Language: | English |
| DOI: | 10.1038/labinvest.2009.19 |
| PUBMED: | 19308045 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: LAINA" - "Source: Scopus" |
