Related Experiment Video
Updated: Jun 18, 2025
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Comparison among different preclinical models derived from the same patient with a non-functional pancreatic
Yan Wang1,2,3,4,5, Zeng Ye1,2,3,4,5, Xin Lou1,2,3,4,5
1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Abstract:
Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.
Insights
Developing new preclinical models for pancreatic neuroendocrine tumors (PNETs) is crucial. Patient-derived xenografts closely mimic human PNETs, offering a valuable platform for research.
Area of Science:
- Oncology
- Translational Research
- Biomedical Engineering
Background:
- Pancreatic neuroendocrine tumors (PNETs) are the second most common pancreatic neoplasms.
- Half of PNET patients develop liver metastases, and current treatments have limited efficacy.
- Scarcity of preclinical models hinders research into PNET molecular mechanisms due to their inert biology.
Purpose of the Study:
- To establish and characterize novel preclinical models for pancreatic neuroendocrine tumors.
- To identify the model that best recapitulates the original human tumor characteristics.
- To provide advanced platforms for studying PNET biology and developing new therapies.
Main Methods:
- Construction of patient-derived organoids and patient-derived xenografts from a single PNET patient.
- Characterization using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing.
- Tumor formation experiments in immunodeficient mice to evaluate model fidelity.
Main Results:
- Successful establishment of patient-derived organoid and patient-derived xenograft models.
- Comprehensive molecular and histological characterization of the models.
- The patient-derived xenograft model demonstrated the highest resemblance to the parental human tumor tissue.
Conclusions:
- Patient-derived xenografts represent a highly accurate preclinical model for pancreatic neuroendocrine tumors.
- These models offer valuable platforms for advancing PNET research and therapeutic development.
- Further investigation using these models can elucidate PNET molecular mechanisms and improve patient outcomes.
