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异种移植部位对人结肠癌干细胞微小RNA表达的影响。

Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells.

作者信息

Mukohyama Junko, Shimono Yohei, Yamashita Kimihiro, Sumi Yasuo, Mukohara Toru, Minami Hironobu, Kakeji Yoshihiro

机构信息

Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

出版信息

Anticancer Res. 2016 Jul;36(7):3679-86.

Abstract

BACKGROUND

Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs.

MATERIALS AND METHODS

Human colon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi-quantitative polymerase chain reaction.

RESULTS

The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs.

CONCLUSION

The xenotransplantation site and the number of tumor passages affect the miRNA expression of human colon CSCs.

摘要

背景

癌症干细胞(CSCs)具有形成患者来源肿瘤异种移植模型(PDXs)的高致瘤能力。PDXs是一种有吸引力的临床前模型,但在PDXs的建立和传代过程中,肿瘤中癌细胞的基因表达和生物学行为会发生变化。

材料与方法

建立人结肠癌PDX,并将其皮下或原位接种到小鼠肠道中进行传代。分析手术标本和PDX的组织学和流式细胞术特征。然后从肿瘤中分离出CSCs,并通过半定量聚合酶链反应分析其微小RNA(miRNA)表达。

结果

手术标本和PDXs在组织学上相似。传代后的PDXs中,CSC群体的大小增加,CSCs中miRNAs的表达发生变化。原位传代的PDXs的CSCs中致癌miRNAs的表达高度上调。

结论

异种移植部位和肿瘤传代次数影响人结肠CSCs的miRNA表达。

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