title: Exploring stemness gene expression and vasculogenic mimicry capacity in well- and poorly-differentiated hepatocellular carcinoma cell lines.
abstract: Vasculogenic mimicry (VM) is the phenomenon where cancer cells mimic endothelial cells by forming blood vessels. A stem cell-like phenotype has been proposed to be involved in this tumor plasticity. VM seems to correlate with metastasis rate, but there have been no reports on the effects of pro-metastatic and pro-angiogenic factors or hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) on VM formation of hepatocellular carcinoma (HCC) cells. Here, we determine VM capacity and expression of stemness genes (Oct4, Sox2, Nanog and CD133) in well- and poorly-differentiated HCC cell lines. The poorly-differentiated cell line SK-Hep-1 with mesenchymal features (high invasiveness and expressing Vimentin, with no E-cadherin) could form VM in vitro, while the well-differentiated cell line HepG2 did not form VM. There was no correlation between expression of stemness genes and intrinsic VM capacity. However, HGF but not VEGF, could induce VM formation in HepG2, concomitant with epithelial-mesenchymal transition (EMT), de-differentiation and increased expression of stemness genes. Our results show that the role of stemness genes in VM capacity of HCC cells is likely to depend on differentiation status.
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Lirdprapamongkol
authors.forename: Khajeelak
authors.initials: K
authors.lastname: Chiablaem
authors.forename: Monnipha
authors.initials: M
authors.lastname: Sila-Asna
authors.forename: Rudee
authors.initials: R
authors.lastname: Surarit
authors.forename: Ahnond
authors.initials: A
authors.lastname: Bunyaratvej
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D010455:Peptides / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015820:Cadherins; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C000606023:PROM1 protein, human; D010455:Peptides; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D017228:Hepatocyte Growth Factor