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肿瘤球来源于前列腺癌细胞,具有化疗耐药性和癌症干细胞特性。

Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

J Cancer Res Clin Oncol. 2012 Apr;138(4):675-86. doi: 10.1007/s00432-011-1146-2. Epub 2012 Jan 12.

Abstract

PURPOSE

Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa, which remains incurable because of the poor understanding of their cell origin and characteristics. We aim to investigate the potential role of cancer stem cells (CSCs) in PCa progression.

METHODS

Human PCa cell lines (LNCaP, 22RV1, DU145 and PC-3) were plated in serum-free suspension culture system allowed for tumorsphere forming. To evaluate the CSC characteristics of tumorspheres, the self-renewal, chemoresistance, tumorigenicity of the PCa tumorsphere cells, and the expression levels of stemness-related proteins in the PCa tumorsphere cells were assessed, comparing with the parental adherent cells.

RESULTS

Tumorsphere cells from PCa cell lines displayed enhanced self-renewal, chemoresistance and tumor-initiating capacity when compared with the adherent cells. Additionally, these cells overexpressed CSC marker CD44. Also, the tumorsphere cells expressed high levels of "stemness" genes Gli1, ABCG2 and Bmi-1.

CONCLUSIONS

Collectively, these data demonstrated that tumorspheres derived from PCa cells possess chemoresistant and CSC properties. Our study suggests that the identification of PCa CSCs could provide new insight into the lethal phenotype of PCa and therapeutic implications.

摘要

目的

当癌细胞发展为去势抵抗性前列腺癌时,前列腺癌(PCa)就会变得致命,由于对其细胞起源和特征的了解不足,这种癌症仍然无法治愈。我们旨在研究癌症干细胞(CSC)在前列腺癌进展中的潜在作用。

方法

将人前列腺癌细胞系(LNCaP、22RV1、DU145 和 PC-3)铺板于无血清悬浮培养系统中,允许形成肿瘤球。为了评估肿瘤球中 CSC 的特征,评估了前列腺癌细胞肿瘤球细胞的自我更新、化疗耐药性、致瘤性,以及与亲本贴壁细胞相比,前列腺癌细胞肿瘤球细胞中干性相关蛋白的表达水平。

结果

与贴壁细胞相比,来自前列腺癌细胞系的肿瘤球细胞表现出增强的自我更新、化疗耐药性和肿瘤起始能力。此外,这些细胞过表达 CSC 标志物 CD44。此外,肿瘤球细胞表达高水平的“干性”基因 Gli1、ABCG2 和 Bmi-1。

结论

综上所述,这些数据表明,源自前列腺癌细胞的肿瘤球具有化疗耐药性和 CSC 特性。我们的研究表明,鉴定前列腺癌 CSC 可以为前列腺癌致命表型提供新的见解,并具有治疗意义。

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