1. Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success
- Author
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SHIMPEI EGUCHI, KENJIRO KIMURA, KEN KAGEYAMA, NAOKI TANI, RYOTA TANAKA, KOHEI NISHIO, HIROJI SHINKAWA, GO OHIRA, RYOSUKE AMANO, SHOGO TANAKA, AKIRA YAMAMOTO, SHIGEKAZU TAKEMURA, MASAKAZU YASHIRO, and SHOJI KUBO
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Endothelial Cells ,General Medicine ,Xenograft Model Antitumor Assays ,Rats ,Pancreatic Neoplasms ,Disease Models, Animal ,Oncology ,Tumor Microenvironment ,Animals ,Heterografts ,Humans ,Carcinoma, Pancreatic Ductal - Abstract
We aimed to investigate the difference in engraftment rates depending on the transplant site for a patient-derived xenograft (PDX) of pancreatic ductal adenocarcinoma (PDAC) and the effects of the microenvironment on engraftment.Frozen cancer tissues from PDAC tumors were used, and tumor fragments were directly implanted into the subcutaneous, orthotopic pancreas, peritoneum, and liver of X-linked severe combined immunodeficiency (XSCID) rats. We assessed the success of engraftment in each organ. Additionally, to evaluate the effect of the microenvironment in each organ, we performed immunohistochemical analysis.Subcutaneous transplantation was successful in 8 of 10 PDAC cases (16 of 30 rats). This was a higher rate than for other organ transplants. The vascular endothelial cells in the stroma were replaced with those from rats instead of humans. Vascular endothelial growth factor-A (VEGF-A) and cluster of differentiation-31 (CD31) was significantly more strongly expressed in the subcutaneous transplantation model (VEGF-A: p0.001, CD31: p=0.0036).The engraftment rate was significantly higher for the subcutaneous PDX model than for the orthotopic pancreatic, peritoneal, and liver PDX models. Blood vessels of the PDX stroma had been replaced by rat-derived vessels instead of the original human vessels, suggesting that angiogenesis in the PDX microenvironment may be a major factor in engraftment.
- Published
- 2022