ArticlePloS one2014
Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Interleukin-1β potentiates transforming growth factor-β-induced fibronectin expression, migration, and invasiveness of mesenchymal-like SK-Hep1 cells via p38 mitogen-activated protein kinase-SMAD2/3 crosstalk.Molecular biology reports · 2026Article
- Noncanonical EZH2 activity cooperates with FOXM1 to drive tumorigenesis and advanced progression in HCC.Clinical and molecular hepatology · 2026Article
- A novel prognostic model for hepatocellular carcinoma based on pyruvate metabolism-related genes.Scientific reports · 2023Article
- Single-cell multiomics reveals heterogeneous cell states linked to metastatic potential in liver cancer cell lines.iScience · 2022Article
- The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma.Cancer medicine · 2022Review
- Estrogen exposure causes the progressive growth of SK-Hep1-derived tumor in ovariectomized mice.Toxicological research · 2022Article
- Article
- Expression and Functionality of Connexin-Based Channels in Human Liver Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Comparison of the [Molecular imaging and biology · 2021Article
- Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Exosomal miR-125b Exerts Anti-Metastatic Properties and Predicts Early Metastasis of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Nuclear receptor FXR impairs SK-Hep-1 cell migration and invasion by inhibiting the Wnt/β-catenin signaling pathway.Oncology letters · 2020Article
- Protein kinase C inhibitors override ZEB1-induced chemoresistance in HCC.Cell death & disease · 2019Article
- The role of magnetic field in the biopharmaceutical production: Current perspectives.Biotechnology reports (Amsterdam, Netherlands) · 2019Review
- Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma.British journal of cancer · 2019Article
- The mitochondrial chaperone Prohibitin 1 negatively regulates interleukin-8 in human liver cancers.The Journal of biological chemistry · 2019Article
- Multipotent mesenchymal stromal cells play critical roles in hepatocellular carcinoma initiation, progression and therapy.Molecular cancer · 2018Review
- Combined Effect of Anticancer Agents and Cytochrome C Decorated Hybrid Nanoparticles for Liver Cancer Therapy.Pharmaceutics · 2018Article
- Translocation of Epidermal Growth Factor (EGF) to the nucleus has distinct kinetics between adipose tissue-derived mesenchymal stem cells and a mesenchymal cancer cell lineage.Journal of structural biology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundSK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. METHODS AND PRINCIPAL
findingsWe found that classical mesenchymal stem cell (MSC) markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC) and bone marrow-derived MSC (BM-MSC) do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC), and that their derivatives also function as CSCs.
conclusionOur findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and metastasis by CSCs of non-epithelial and endothelia origin.
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