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

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Authors: Sung Hoon Choi ; Sang Woo Lee ; Minseon Ok ; Kyung Sik Kim ; Sungsik Kim ; Sang Hoon Ahn

MeSH: Carcinoma, Hepatocellular/genetics* ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Gene Expression Profiling* ; Gene Expression Regulation, Neoplastic* ; Humans ; Hypoxia/complications* ; Hypoxia/genetics ; Liver Neoplasms/genetics* ; Liver Neoplasms/pathology* ; Neoplasm Recurrence, Local/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results

Keywords: Hypoxia ; cancer stem cell ; hepatocellular carcinoma ; microarray

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.