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肾癌干细胞的生物标志物发现

Biomarker discovery for renal cancer stem cells.

作者信息

Corrò Claudia, Moch Holger

机构信息

Department of Pathology and Molecular PathologyUniversity Hospital ZurichSwitzerland.

出版信息

J Pathol Clin Res. 2018 Jan 17;4(1):3-18. doi: 10.1002/cjp2.91. eCollection 2018 Jan.

Abstract

Characterised by high intra- and inter-tumor heterogeneity, metastatic renal cell carcinoma (RCC) is resistant to chemo- and radiotherapy. Therefore, the development of new prognostic and diagnostic markers for RCC patients is needed. Cancer stem cells (CSCs) are a small population of neoplastic cells within a tumor which present characteristics reminiscent of normal stem cells. CSCs are characterised by unlimited cell division, maintenance of the stem cell pool (self-renewal), and capability to give rise to all cell types within a tumor; and contribute to metastasis (tumourigenicity), treatment resistance and recurrence. So far, many studies have tried to establish unique biomarkers to identify CSC populations in RCC. At the same time, different approaches have been developed with the aim to isolate CSCs. Consequently, several markers were found to be specifically expressed in CSCs and cancer stem-like cells derived from RCC such as CD105, ALDH1, OCT4, CD133, and CXCR4. However, the contribution of genetic and epigenetic mechanisms, and tumor microenvironment, to cellular plasticity have made the discovery of unique biomarkers a very difficult task. In fact, contrasting results regarding the applicability of such markers to the isolation of renal CSCs have been reported in the literature. Therefore, a better understanding of the mechanism underlying CSC may help dissecting tumor heterogeneity and drug treatment efficiency.

摘要

转移性肾细胞癌(RCC)具有高度的肿瘤内和肿瘤间异质性,对化疗和放疗具有抗性。因此,需要为RCC患者开发新的预后和诊断标志物。癌症干细胞(CSCs)是肿瘤内一小群具有类似正常干细胞特征的肿瘤细胞。CSCs的特征在于无限的细胞分裂、干细胞池的维持(自我更新)以及产生肿瘤内所有细胞类型的能力;并导致转移(致瘤性)、治疗抗性和复发。到目前为止,许多研究试图建立独特的生物标志物来识别RCC中的CSC群体。同时,已经开发了不同的方法来分离CSCs。因此,发现几种标志物在CSCs和源自RCC的癌症干细胞样细胞中特异性表达,如CD105、ALDH1、OCT4、CD133和CXCR4。然而,遗传和表观遗传机制以及肿瘤微环境对细胞可塑性的影响使得发现独特的生物标志物成为一项非常困难的任务。事实上,文献中报道了关于此类标志物在分离肾CSCs中的适用性的矛盾结果。因此,更好地理解CSC的潜在机制可能有助于剖析肿瘤异质性和药物治疗效果。

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