Hepatoma SK Hep-1 Cells Exhibit Characteristics of Oncogenic Mesenchymal Stem Cells with Highly Metastatic Capacity

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.

Combined Effect of Anticancer Agents and Cytochrome C Decorated Hybrid Nanoparticles for Liver Cancer Therapy

“…We believe this may be due to the fact that they do not possess any mRNA of hepatic-specific proteins (albumin and fibrinogen) or due to a difference in proliferation rate or cellular uptake mechanism of drugs/particles compared with the other cell lines [23]. Hence, in these highly resistant cells, we did not observe any IC 50 when incubated with all the drug molecules except doxorubicin.…”

Autoregulatory loop of nuclear corepressor 1 expression controls invasion, tumor growth, and metastasis

“…mRNAs of selected prometastatic genes, including cyclooxigenase 2 (COX2), DNA-binding protein inhibitor 1 (ID1), C-MET, matrix metallopeptidase (MMP)2, MMP9, CXCR4, CCR1, CCR6, and CCR7, were measured in SK-hep1 (SK) cells transfected with a control siRNA or with an NCoR-specific siRNA. These cells were derived from a patient with liver adenocarcinoma and recently have been shown to have an oncogenic mesenchymal stem cell phenotype (32). Most of these genes were significantly increased upon NCoR depletion in SK cells (Fig.…”

Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma

“…Our results showed that CA suppressed cell proliferation and induced apoptosis in SK‐Hep‐1 cells. SK‐Hep‐1 cells possess aggressive migration and metastatic properties, which has been considered with mesenchymal origin characteristics . While the different tumor pathology between SK‐Hep‐1 cells (mesenchymal type) and hepatocytes (epithelial type), Eun et al demonstrates that SK‐Hep‐1 cells represent a transformation mechanism of mesenchymal stem cell into an enhanced self‐renewal cancer stem cells .…”

“…SK‐Hep‐1 cells possess aggressive migration and metastatic properties, which has been considered with mesenchymal origin characteristics . While the different tumor pathology between SK‐Hep‐1 cells (mesenchymal type) and hepatocytes (epithelial type), Eun et al demonstrates that SK‐Hep‐1 cells represent a transformation mechanism of mesenchymal stem cell into an enhanced self‐renewal cancer stem cells . Thus, SK‐Hep‐1 cells are very critical cell lines applied in investigation, and the fact that the properties of the SK‐Hep‐1 cell line can be maintained in culture conditions and in vivo models makes it more suitable for HCC studies.…”