Orthotopic inflammation-related pancreatic carcinogenesis in a wild-type mouse induced by combined application of caerulein and dimethylbenzanthracene.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies, with a poor long-term prognosis, and effective therapeutic options are lacking. Observing the dynamics of the pathogenesis of pancreatic intraepithelial neoplasia (PanIN) and PDAC in tumor models can facilitate understanding of the molecular mechanisms involved in early PDAC. Furthermore, it can compensate for the research limitations associated with analyzing clinical specimens of late-stage PDAC. In this study, we orthotopically treated the pancreas with dimethylbenzanthracene (DMBA) combined with caerulein in wild-type C57BL/6 J mice to induce inflammation-related pancreatic carcinogenesis. We observed that DMBA and caerulein treatment induced a chronic consumptive disease, which caused a decrease in the relative body and pancreas weights, diminishing the health status of the mice and enhancing the inflammation-related histological changes. Moreover, mid-dose and high-frequency treatment with caerulein caused prolonged inflammatory damage to the pancreas and contributed to a permissive environment for the development of PDAC. CXCL12/CXCR4, CCL2/CCR2, and several cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were upregulated in the tumor tissue of DMBA and caerulein-induced PDAC mice. This orthotopic mouse pancreatic carcinogenesis model mimic human disease because it reproduces a spectrum of pathological changes observed in human PDAC, ranging from inflammatory lesions to pancreatic intraepithelial neoplasia. Thus, this mouse model may improve the understanding of molecular mechanisms underlying the injury-inflammation-cancer pathway in the early stages of pancreatic carcinogenesis.
Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chen
C
Liang
Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Zhen
Z
Wang
Department of Image, Fudan University Shanghai Zhongshan Hospital, Shanghai Medical College, Shanghai, China.
Li
L
Wu
Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chen
C
Wang
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Bao-Hua
BH
Yu
Department of Image, Fudan University Shanghai Zhongshan Hospital, Shanghai Medical College, Shanghai, China.
Xiu-Zhong
XZ
Yao
Department of Image, Fudan University Shanghai Zhongshan Hospital, Shanghai Medical College, Shanghai, China.
Xiao-Lin
XL
Wang
Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China. liyingyi@fudan.edu.cn.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. liyingyi@fudan.edu.cn.
Ying-Yi
YY
Li
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002108:Ceruletide / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D002108:Ceruletide
Caerulein; DMBA; Pancreatic cancer; Pancreatitis