Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success
Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success
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DOI：
10.21873/anticanres.15718
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发表时间：
2022-04
影响因子：
2
通讯作者：
Shimpei Eguchi;K. Kimura;Ken Kageyama;Naoki Tani;Ryota Tanaka;K. Nishio;H. Shinkawa;G. Ohira;R. Amano;Shogo Tanaka;Akira Yamamoto;S. Takemura;M. Yashiro;S. Kubo
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作者：
Shimpei Eguchi;K. Kimura;Ken Kageyama;Naoki Tani;Ryota Tanaka;K. Nishio;H. Shinkawa;G. Ohira;R. Amano;Shogo Tanaka;Akira Yamamoto;S. Takemura;M. Yashiro;S. Kubo
背景资料：我们的目的是研究胰腺导管腺癌（PDAC）患者源性异种移植物（PDX）移植部位不同的植入率差异以及微环境对植入的影响。材料与方法：使用PDAC肿瘤的冷冻癌组织，并将肿瘤碎片直接植入X连锁严重联合免疫缺陷（XSCID）大鼠的皮下、原位胰腺、腹膜和肝脏。我们评估了每个器官的植入成功率。此外，为了评估每个器官中微环境的影响，我们进行了免疫组织化学分析。结果：10例PDAC中8例（30只大鼠中16只）皮下移植成功。这一比例高于其他器官移植。基质中的血管内皮细胞被大鼠而不是人类的血管内皮细胞所取代。血管内皮生长因子-A（VEGF-A）和分化簇-31（CD 31）在皮下移植模型中显著更强地表达（VEGF-A：p<0.001，CD 31：p=0.0036）。结论：皮下PDX模型的植入率显著高于原位胰腺、腹膜和肝脏PDX模型。PDX间质的血管已被大鼠来源的血管取代，而不是原来的人血管，这表明PDX微环境中的血管生成可能是植入的主要因素。
Background: 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. Materials and Methods: 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. Results: 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: p<0.001, CD31: p=0.0036). Conclusion: 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.