Hepatocellular Carcinoma-propagating Cells are Detectable by Side Population Analysis and Possess an Expression Profile Reflective of a Primitive Origin
Autor: | Wei-Hua Ren, Wei-Dong Jia, Honghai Xia, Qingyu Cheng, Geliang Xu, Xiaoyuan Song, Yang Lv, Jun Cao, Qing Li |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Carcinoma Hepatocellular Kruppel-Like Transcription Factors Mice SCID Biology Stem cell marker Article Transcriptome Kruppel-Like Factor 4 Mice 03 medical and health sciences Side population Cancer stem cell SALL4 medicine Animals Humans Side-Population Cells Cell Proliferation Multidisciplinary Microarray analysis techniques HMGA2 Protein Liver Neoplasms Hep G2 Cells Molecular biology digestive system diseases Gene Expression Regulation Neoplastic 030104 developmental biology CCAAT-Binding Factor KLF4 Neoplastic Stem Cells Heterografts Stem cell Transcription Factors |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep34856 |
Popis: | The recent identification of “Side Population” (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 102 cells/mouse). The mRNA microarray analysis of the SP vs. NSP cells isolated from HepG2 cells revealed that the SP cells express higher levels of pluripotency- and stem cell-associated transcription factors including Klf4, NF-Ya, SALL4 and HMGA2. Some of the known hepatobiliary progenitor/stem cell markers, such as Sox9 was also up-regulated. RT-qPCR analysis of the gene expression between SP cells and NSP cells isolated from both HepG2 cells and HCC tissue samples showed that most of the tested mRNAs’ changes were in consistent with the microarray data, including the general progenitor/stem cells markers such as Klf4, NF-Ya, SALL4 and HMGA2, which were up-regulated in SP cells. Our data indicates that HCC cancer stem cells exist in HepG2 and HCC fresh tissue samples and can be isolated by SP assay. |
Databáze: | OpenAIRE |
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