Abstract
The roles of inflammatory macrophages in pancreatic tissue and the development of pancreatic cancer have not been well characterized. Recently it was shown that inflammatory macrophages, besides their function in clearing dead cells, also initiate pancreatic acinar cell metaplasia to duct-like progenitor cells. While in pancreatitis this is a reversible process, in context of an oncogenic stimulus this process is irreversible and can lead to the formation of precancerous lesions. Recent work now indicates that acquisition of an activating Kras mutation in acinar cells initiates signaling that leads to chemoattraction of M1-poliarized macrophages. This oncogene-caused chronic microinflammation can accelerate the pathogenesis of pancreatic cancers.
Highlights
Infiltration of macrophages into the pancreas occurs during acute or chronic pancreatitis; and chronic pancreatitis is tightly-linked to development and progression of pancreatic ductal adenocarcinoma (PDA)
The view on M1 macrophages changed with recent publications showing that M1-polarized macrophages can initiate and drive acinar cell transdifferentiation to a duct-like progenitor cell type, a process called acinarto-ductal metaplasia (ADM) [2]
This may be explained by the constant presence of macrophages generating an ADM cell type [2, 3], since these progenitor cells in presence of proto-oncogenic signaling can progress to a pre-neoplastic cell type such as the one forming pancreatic intraepithelial neoplasia (PanIN) [12]
Summary
Infiltration of macrophages into the pancreas occurs during acute or chronic pancreatitis; and chronic pancreatitis is tightly-linked to development and progression of pancreatic ductal adenocarcinoma (PDA). These ADM progenitor cells in context of oncogenic signaling (Kras mutation or augmented EGF-R) initiate the formation of pancreatic lesions and eventually development of PDA [3]. Acinar-to-ductal metaplasia generates a cellular phenotype that expresses markers for pancreatic progenitor cells.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
