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Activated Pancreatic Stellate Cells Enhance the Warburg Effect to Cause the Malignant Development in Chronic Pancreatitis
- Source :
- Frontiers in Oncology, Frontiers in Oncology, Vol 11 (2021)
- Publication Year :
- 2021
-
Abstract
- Chronic pancreatitis (CP) is a precancerous condition associated with pancreatic ductal adenocarcinoma (PDAC), but its evolutionary mechanism is unclear. Pancreatic stellate cells (PSCs) are closely related to the occurrence and development of CP and PDAC, but it is not clear whether PSCs play a key role in this “inflammation-cancer transition”. Our research found that co-culture with activated PSCs promoted the proliferation, migration and invasion of normal pancreatic duct epithelial cells and pancreatic cancer cells. At the same time, activated PSCs had a significant effect on the expression of the glycolysis markers (pyruvate kinase M2, lactate dehydrogenase A, glucose transporter 1, hexokinase-II and monocarboxylate transporter 4; PKM2, LDHA, GLUT1, HK2 and MCT4) in normal pancreatic duct epithelial cells and pancreatic cancer cells and increased lactic acid production and glucose consumption in these two cells. In vivo experiments showed that the expression of the glycolysis markers in pancreatic duct epithelial cells and the marker protein (α-SMA) of activated PSCs in the pancreatic duct peripancreatic interstitium were higher in pancreatic cancer tissues and chronic pancreatitis tissues than in normal pancreatic tissues in both animals and humans. In addition, analysis of human tissue specimens showed that there is a correlation between the expression of glycolysis markers and α-SMA. These findings indicate that activated PSCs play an important role in the development and progression of chronic pancreatitis into pancreatic cancer by regulating and promoting aerobic glycolysis. Our research provides a new theoretical basis for further understanding the mechanism of CP malignancy and the selection of targets for reversing CP malignancy.
- Subjects :
- Cancer Research
activated pancreatic stellate cells
Lactate dehydrogenase A
pancreatic ductal adenocarcinoma
PKM2
Pancreatic cancer
medicine
education
RC254-282
Original Research
Pancreatic duct
education.field_of_study
biology
malignant development in chronic pancreatitis
Chemistry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Warburg effect
co-culture
medicine.anatomical_structure
Oncology
Anaerobic glycolysis
the Warburg effect
Monocarboxylate transporter 4
biology.protein
Cancer research
Pancreatitis
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in oncology
- Accession number :
- edsair.doi.dedup.....3ff5d19e0b3fbf3a4195a2c97830836b