Novel orthotopic patient-derived xenograft model using human pancreatic cancer tissue fragments to recapitulate distant metastasis and cancer-related hypercoagulability

被引:0
作者
Miura, Takuma [1 ]
Watanabe, Arisa [1 ]
Miyake, Mutsumi [1 ]
Suga, Sayaka [2 ]
Miyoshi, Makoto [1 ]
Miyashita, Kumiko [1 ]
Komatsu, Shohei [3 ]
Nishimura, Noriyuki [1 ]
Shimizu, Kazuya [1 ,4 ]
Hori, Yuichi [1 ]
机构
[1] Kobe Univ, Grad Sch Hlth Sci, Dept Biophys, 7-10-2 Tomogaoka,Suma Ku, Kobe 6540142, Japan
[2] Kobe Univ, Grad Sch Hlth Sci, Dept Nursing, Kobe, Japan
[3] Kobe Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Kobe, Japan
[4] Natl Hosp Org Kobe Med Ctr, Dept Internal Med, Kobe, Japan
基金
日本学术振兴会;
关键词
Pancreatic cancer; Patient-derived xenograft (PDX); Orthotopic transplantation; Metastasis; Trousseau's syndrome; GEMCITABINE; RESISTANCE;
D O I
10.1007/s00795-025-00425-3
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pancreatic cancer is a malignant tumor that metastasizes to distant organs, such as the liver and lungs from an early stage. Few animal models can reproduce early metastasis. In addition, no model has been reported that reproduces cancer-related hypercoagulability, which is characteristic of pancreatic ductal adenocarcinoma and other adenocarcinomas. We hypothesized that the reason why the commonly used orthotopic cell xenograft model cannot reproduce the disease is inadequate construction of the cancer microenvironment. We developed an orthotopic tissue fragment xenograft model in which tumor tissue was transplanted into the pancreas of mice while preserving the microenvironment. Briefly, we injected single cancer cells subcutaneously to form a tumor, which was then cut with a scalpel into tumor fragments. A fragment was then sutured and fixed to the surface of the pancreatic tail. In this study, we evaluated the superiority of this model over a conventional orthotopic cell xenograft model. As a result, the novel orthotopic tissue xenograft model reproduced early distant metastasis to the liver and lung, nerve invasion, and cancer-related hypercoagulability of human pancreatic cancer, and showed greater similarity to clinical cases than the control orthotopic cell xenograft model.
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页数:10
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