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Published on: November 19, 2019
What are the macrophages and stellate cells doing in pancreatic adenocarcinoma?
Stephen J Pandol1, Mouad Edderkaoui1
1Departments of Medicine and Biological Sciences, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles Los Angeles, CA, USA.
Abstract:
Pancreatic ductal adenocarcinoma is a devastating disease characterized by a dense desmoplastic stroma. Chemo- and radio-therapeutic strategies based on targeting cancer cells have failed in improving the outcome of this cancer suggesting important roles for stroma in therapy resistance. Cells in the tumor stroma have been shown to regulate proliferation, resistance to apoptosis and treatments, epithelial to mesenchymal transition (EMT) and stemness of cancer cells. Stellate cells in their activated state have been thought over the past decade to only have tumor promoting roles. However, recent findings suggest that stellate cells may have protective roles as well. The present review highlights the latest findings on the role of two major components of tumor stroma, pancreatic stellate cells and macrophages, in promoting or inhibiting pancreatic cancer, focused on their effects on EMT and cancer stemness.
Insights
Pancreatic cancer
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is marked by a dense desmoplastic stroma.
- Conventional therapies targeting cancer cells show limited efficacy, indicating the stroma's role in treatment resistance.
- Tumor stroma components influence cancer cell proliferation, apoptosis resistance, epithelial-to-mesenchymal transition (EMT), and stemness.
Purpose of the Study:
- To review current findings on the dual role of pancreatic stellate cells and macrophages in pancreatic cancer.
- To focus on how these stromal cells affect EMT and cancer stemness in PDAC.
Main Methods:
- Literature review of recent studies on pancreatic cancer stroma.
- Analysis of the roles of pancreatic stellate cells and macrophages.
- Examination of their impact on epithelial-to-mesenchymal transition and cancer stemness.
Main Results:
- Pancreatic stellate cells and macrophages can promote or inhibit pancreatic cancer progression.
- These stromal cells significantly influence cancer cell EMT and stemness.
- Emerging evidence suggests potential protective roles for activated stellate cells.
Conclusions:
- Stromal cells, particularly pancreatic stellate cells and macrophages, are critical regulators in pancreatic cancer.
- Understanding their complex roles in EMT and stemness is vital for developing effective therapeutic strategies.
- Further research into the context-dependent functions of these stromal cells may reveal new treatment avenues.
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