AI Article Synopsis
- Defensins are important antimicrobial peptides related to innate immunity, cell regeneration, and cancer development, and this study examines their role in pancreatic ductal adenocarcinoma (PDAC) associated with chronic pancreatitis (CP).
- The research involved analyzing human pancreatic tissues for defensin α 1 (HNP-1) through various methods, confirming its expression in PDAC and CP tissues and studying its behavior in cancer and normal cells influenced by proinflammatory cytokines.
- Findings showed increased levels of HNP-1 in malignant pancreatic cells and its regulation by inflammation, suggesting that HNP-1 may connect chronic inflammation to the development of pancreatic cancer.
Article Abstract
Objectives: Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP).
Methods: Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE).
Results: Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels.
Conclusions: Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.
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| http://dx.doi.org/10.1097/MPA.0000000000001054 | DOI Listing |
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