The crosstalk between acinar cells with Kras mutations and M1-polarized macrophages leads to initiation of pancreatic precancerous lesions

Oncoimmunology. 2015 Mar 19;4(6):e1008794. doi: 10.1080/2162402X.2015.1008794. eCollection 2015 Jun.

Abstract

Recent studies on the processes that lead to the development of pancreatic cancer indicate that inflammatory macrophages have key functions in the initiation of pre-neoplastic lesions. Specifically, acquisition of an activating Kras mutation in pancreatic acinar cells leads to upregulation of intercellular adhesion molecule-1 (ICAM-1), which serves as a chemoattractant for M1-polarized macrophages. M1 macrophages then contribute to acinar cell metaplasia and development of precancerous lesions through inflammatory cytokines and secreted proteases.

Keywords: Kras; PanIN; acinar-to-ductal metaplasia; inflammation; macrophages; pancreas; pancreatic cancer; pancreatitis.