Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar 28;2(3):247-51.
doi: 10.18632/oncoscience.151. eCollection 2015.

Inflammatory macrophages in pancreatic acinar cell metaplasia and initiation of pancreatic cancer

Geou-Yarh Liou  1 , Peter Storz  1
Affiliations

Inflammatory macrophages in pancreatic acinar cell metaplasia and initiation of pancreatic cancer

Geou-Yarh Liou et al. Oncoscience. .

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.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Inflammatory macrophages drive the ADM process during acute pancreatitis
During acute pancreatitis acinar cells can either undergo cell death or a transdifferentiation process named acinar-to-ductal metaplasia (ADM). ADM changes their phenotype to pancreatic progenitor-like cells, which could be important for pancreatic repopulation. Inflammatory macrophages can initiate ADM through release of cytokines and chemokines. They also regulate removal of dead cells and modulation of the microenviroment. The net effect of these different functions of inflammatory macrophages possibly leads to pancreatic regeneration.
Figure 2
Figure 2. M1-polarized macrophages contribute to the initiation of pre-neoplastic lesions
Acinar cells that acquire an activating Kras mutation (i.e. KrasG12D) can cause microinflammation by expressing chemoattractants for M1 macrophages. M1 macrophages then drive ADM and the formation of pre-neoplastic lesions by providing cytokines, chemokines and proteinases that modulate pancreatic microenvironment.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hao NB, Lu MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol. 2012;2012:948098. - PMC - PubMed
    1. Liou GY, Doppler H, Necela B, Krishna M, Crawford HC, Raimondo M, Storz P. Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-kappaB and MMPs. J Cell Biol. 2013;202(3):563–577. - PMC - PubMed
    1. Liou GY, Doppler H, Necela B, Edenfield B, Zhang L, Dawson DW, Storz P. Mutant Kras-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions. Cancer Discov. 2014 - PMC - PubMed
    1. Forsmark CE. Management of chronic pancreatitis. Gastroenterology. 2013;144(6):1282–1291 e1283. - PubMed
    1. Gea-Sorli S, Closa D. Role of macrophages in the progression of acute pancreatitis. World J Gastrointest Pharmacol Ther. 2010;1(5):107–111. - PMC - PubMed

LinkOut - more resources