title: Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.
abstract: BACKGROUND
  SK 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America; Department of Internal Medicine, Yeungnam University College Medicine, Daegu, Korea.
authors.forename: Jong Ryeol
authors.initials: JR
authors.lastname: Eun
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America; Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America; School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tschudy-Seney
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Rajen
authors.initials: R
authors.lastname: Ramsamooj
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
authors.affiliation: Department of Pathology and Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York, United States of America.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zern
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, United States of America; Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: Yuyou
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000556:secondary*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D059467:Transcriptome