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Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage–stellate cell interaction
- Source :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Pancreatic cancer occurs in the setting of a profound fibrotic microenvironment that often dwarfs the actual tumor. Although pancreatic fibrosis has been well studied in chronic pancreatitis, its development in pancreatic cancer is much less well understood. This article describes the dynamic remodeling that occurs from pancreatic precursors (pancreatic intraepithelial neoplasias (PanINs)) to pancreatic ductal adenocarcinoma, highlighting similarities and differences between benign and malignant disease. Although collagen matrix is a commonality throughout this process, early stage PanINs are virtually free of periostin while late stage PanIN and pancreatic cancer are surrounded by an increasing abundance of this extracellular matrix protein. Myofibroblasts also become increasingly abundant during progression from PanIN to cancer. From the earliest stages of fibrogenesis, macrophages are associated with this ongoing process. In vitro co-culture indicates there is cross-regulation between macrophages and pancreatic stellate cells (PaSCs), precursors to at least some of the fibrotic cell populations. When quiescent PaSCs were co-cultured with macrophage cell lines, the stellate cells became activated and the macrophages increased cytokine production. In summary, fibrosis in pancreatic cancer involves a complex interplay of cells and matrices that regulate not only the tumor epithelium but the composition of the microenvironment itself.
- Subjects :
- Pathology
medicine.medical_specialty
Periostin
Biology
Article
Cell Line
Pathology and Forensic Medicine
Extracellular matrix
Mice
Fibrosis
Pancreatic cancer
medicine
Animals
Macrophage
Pancreas
Molecular Biology
Metaplasia
Macrophages
Pancreatic Stellate Cells
Cancer
Receptor Cross-Talk
Cell Biology
medicine.disease
3. Good health
Pancreatic Neoplasms
Disease Models, Animal
Disease Progression
Hepatic stellate cell
Pancreatitis
Carcinoma, Pancreatic Ductal
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Laboratory Investigation
- Accession number :
- edsair.doi.dedup.....c68cc62a8507e08c4f3c069de857116b