Establishment of pancreatic cancerogenesis model in immunocompetent mice and the changes of immune cell populations

Qiaofei Liu ,Zhaohui Lü ,Yuan Li ,Mengyi Wang ,Quan Liao ,Zheyu Niu ,Lutian Yao ,Yupei Zhao

doi:10.3760/cma.j.issn.1674-6090.2016.03.003

Abstract

Objective To establish the pancreatic cancerogenesis model in mice and to observe the changes of the immune cell populations in peripheral blood and pancreatic lesions. Methods The in situ embedding of canerogen dimethylbenzanthracene (DMBA) was adopted to establish the pancreatic cancerogenesis process from chronic pancreatitis (CP) , pancreatic intraepithelial neoplasma (PanIN) to pancreatic cancer. Totally 60 C57BL/6J mice were used, and 8 weeks after embedding, the mice were killed. 20 mice were randomized selected, and 7 immune cell populations in the peripheral blood and pancreatic lesions were detected by flow cytometery (FCM) . Results During the observational peroid of 8 weeks, 14 (23.3%) mice died. Among the 46 survivors, 20 mice were randomized selected for FCM analysis. All of the 46 pancreatic lesions were pathologically analyzed. 12 cases were CP (26.1%) , 11 cases were lower grade PanIN (PanIN-1,2, LG-PanIN) (23.9%) , 9 cases were high grade PanIN (PanIN-3, HG-PanIN) (19.6%) and 14 cases were PC. Among the 20 randomized selected mice, 4 cases were CP, 7 cases were LG-PanIN, 4 cases were HG-PanIN and 5 cases were PC. The myeloid derived suppressor cells (MDSC) of HG-PanIN and CP were significantly more than that of LG-PanIN and CP. In the pancreatic lesions, the granulocytes, MDSC and M2 polarized TAM of HG-PanIN and PC were significantly more than that of LG-PanIN and CP. On the contrary, the T lymphocytes and M1 polarized TAM were significantly decreased. Conclusions In situ embedding of DMBA is a feasible and practical method to establish the spontaneous pancreatic cancerogenesis model in the immunocompetent mice. Pancreatic cancerogenesis can induce systemic and even stronger local immunosuppression, and the MDSC and M2 polarized TAM may play the vital roles. Key words: Pancreatic Cancer; Cancerogenesis; Immunosuppression; Myeloid-derived suppressor cells; Tumor associated macrophages

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