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缺氧条件下肝癌来源的癌干细胞样细胞的基因表达谱分析

Gene Expression Profiling of Hepatocellular Carcinoma Derived Cancer Stem Like Cell under Hypoxia.

作者信息

Choi Sung Hoon, Lee Sang Woo, Ok Minseon, Kim Kyung Sik, Kim Sungsik, Ahn Sang Hoon

机构信息

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Division of Bioconvergence, Drug and Disease Target Group, Korea Basic Science Institute, Ochang, Korea.

出版信息

Yonsei Med J. 2017 Sep;58(5):925-933. doi: 10.3349/ymj.2017.58.5.925.

DOI:10.3349/ymj.2017.58.5.925
PMID:28792135
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5552646/
Abstract

PURPOSE

Cancer stem like cells (CSCs), with unlimited self-renewal potential and other stem cell characteristics, occur in several cancers including hepatocellular carcinoma (HCC). Although CSCs can initiate tumors, malignant proliferation, relapse and multi-drug resistance, the ways how to activate them still remain unknown. This study aims to evaluate whether CSC acquire tumorigenic characters under tumor hypoxia, analyzed by microarray analysis.

MATERIALS AND METHODS

CSCs were purified from HCC patients and Affymetrix microarray was used to investigate their gene expression profiles. The results were validated by real-time polymerase chain reaction (PCR).

RESULTS

The results of the microarray indicated that 18 genes were up-regulated and 10 genes were down-regulated in CSCs. Several genes were identified to be significantly involved in the regulation of CSCs such as HCC. Furthermore, the up-regulated genes were related with metabolism, angiogenesis and hypoxia, whereas the down-regulated genes were related with apoptosis and inflammation.

CONCLUSION

The results may help to understand the mechanisms of tumor development through CSCs which acquired their distinctive tumorogenic properties by hypoxic stimulation.

摘要

目的

癌症干细胞(CSCs)具有无限自我更新潜能及其他干细胞特征,存在于包括肝细胞癌(HCC)在内的多种癌症中。尽管癌症干细胞能够引发肿瘤、恶性增殖、复发及多药耐药,但激活它们的方式仍不清楚。本研究旨在通过微阵列分析评估癌症干细胞在肿瘤缺氧条件下是否获得致瘤特性。

材料与方法

从肝癌患者中纯化出癌症干细胞,利用Affymetrix微阵列研究其基因表达谱。结果通过实时聚合酶链反应(PCR)进行验证。

结果

微阵列结果表明,癌症干细胞中有18个基因上调,10个基因下调。鉴定出几个基因显著参与癌症干细胞如肝癌的调控。此外,上调基因与代谢、血管生成和缺氧相关,而下调基因与凋亡和炎症相关。

结论

这些结果可能有助于理解通过癌症干细胞发生肿瘤发展的机制,癌症干细胞通过缺氧刺激获得其独特的致瘤特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/47f147d83c8a/ymj-58-925-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/726de854e60e/ymj-58-925-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/7db4fc6d9cf2/ymj-58-925-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/b2337b4450cf/ymj-58-925-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/47f147d83c8a/ymj-58-925-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/726de854e60e/ymj-58-925-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/7db4fc6d9cf2/ymj-58-925-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/b2337b4450cf/ymj-58-925-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/5552646/47f147d83c8a/ymj-58-925-g004.jpg

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Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia-inducible factors HIF1α and HIF2α.耐药性与癌症干细胞:缺氧诱导因子HIF1α和HIF2α的共同但不同的作用
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癌症干细胞:肝癌靶向治疗的潜在突破
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ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models.整合素α6(ITGA6)受缺氧诱导因子直接调控,并在转移性乳腺癌模型中富集,以促进癌症干细胞活性和侵袭。
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