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基于细胞学的基因突变人胰腺癌细胞异种移植模型中循环肿瘤细胞的检测。

Cytology-based Detection of Circulating Tumour Cells in Human Pancreatic Cancer Xenograft Models With Mutation.

机构信息

Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan

Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan.

出版信息

Anticancer Res. 2020 Dec;40(12):6781-6789. doi: 10.21873/anticanres.14701.

Abstract

BACKGROUND/AIM: To examine the dynamics of circulating tumour cells (CTCs) in pancreatic cancer (PC), new mouse CTC models from human PC xenografts were developed.

MATERIALS AND METHODS

Orthotopic (pancreas) and heterotopic (subcutaneous) transplantation models using GFP-tagged SUIT-2 PC cells were prepared. Using a cytology-based CTC detection platform, CTCs and metastasis were compared.

RESULTS

The two types of orthotopic models, including the surgical transplantation model and the intraperitoneal injection model, showed a similar pattern of initial pancreatic tumour formation and subsequent development of peritoneal and hematogenous lung metastases. In the heterotopic model, only hematogenous lung metastasis was observed, and the number of CTCs and lung metastases was higher than that of the orthotopic model. Furthermore, KRAS mutation (G12D) was detected in CTCs.

CONCLUSION

These orthotopic and heterotopic models clearly differ in terms of the pattern of metastasis and CTCs and therefore, would be useful PC models to investigate the effect of drug-therapy on CTCs and the role of KRAS mutation.

摘要

背景/目的:为了研究胰腺导管腺癌(PC)中循环肿瘤细胞(CTC)的动态变化,我们建立了源自人 PC 异种移植物的新型小鼠 CTC 模型。

材料和方法

使用 GFP 标记的 SUIT-2 PC 细胞建立了原位(胰腺)和异位(皮下)移植模型。利用基于细胞学的 CTC 检测平台,比较了 CTC 和转移情况。

结果

两种类型的原位模型,包括手术移植模型和腹腔注射模型,表现出相似的初始胰腺肿瘤形成模式,随后发展为腹膜和血源性肺转移。在异位模型中,仅观察到血源性肺转移,CTC 和肺转移的数量高于原位模型。此外,在 CTC 中检测到 KRAS 突变(G12D)。

结论

这些原位和异位模型在转移模式和 CTC 方面存在明显差异,因此将成为研究药物治疗对 CTC 影响以及 KRAS 突变作用的有用 PC 模型。

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