Inflammation Associated Pancreatic Tumorigenesis: Upregulation of Succinate Dehydrogenase (Subunit B) Reduces Cell Growth of Pancreatic Ductal Epithelial Cells
| Autor: | Bence Sipos, Christoph Röcken, N Ammar, Karin Schwarz, Julia Luisa Möller, Susanne Sebens, Sascha Rahn, Daniela Wesch, T Demetrowitsch, Ole Helm, Heiner Schäfer, Philippe Dänzer Barbosa |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
SDHB pancreatic cancer Inflammation medicine.disease_cause Sdhb Article inflammatory stroma chronic pancreatitis Downregulation and upregulation Pancreatic cancer medicine ddc:6 ddc:610 Gene knockdown Chemistry Cell growth Macrophages article medicine.disease macrophages Oncology Inflammatory Stroma Cancer research Immunohistochemistry medicine.symptom Carcinogenesis Chronic pancreatitis |
| Zdroj: | Cancers Volume 12 Issue 1 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12010042 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is amongst the most fatal malignancies and its development is highly associated with inflammatory processes such as chronic pancreatitis (CP). Since the succinate dehydrogenase subunit B (SDHB) is regarded as tumor suppressor that is lost during cancer development, this study investigated the impact of M1-macrophages as part of the inflammatory microenvironment on the expression as well as function of SDHB in benign and premalignant pancreatic ductal epithelial cells (PDECs). Immunohistochemical analyses on pancreatic tissue sections from CP patients and control individuals revealed a stronger SDHB expression in ducts of CP tissues being associated with a greater abundance of macrophages compared to ducts in control tissues. Accordingly, indirect co-culture with M1-macrophages led to clearly elevated SDHB expression and SDH activity in benign H6c7-pBp and premalignant H6c7-kras PDECs. While siRNA-mediated SDHB knockdown in these cells did not affect glucose and lactate uptake after co-culture, SDHB knockdown significantly promoted PDEC growth which was associated with increased proliferation and decreased effector caspase activity particularly in co-cultured PDECs. Overall, these data indicate that SDHB expression and SDH activity are increased in PDECs when exposed to pro-inflammatory macrophages as a counterregulatory mechanism to prevent excessive PDEC growth triggered by the inflammatory environment. |
| Databáze: | OpenAIRE |
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