title: Expression of intercellular adhesion molecule 1 by hepatocellular carcinoma stem cells and circulating tumor cells.
abstract: OBJECTIVE
  Intercellular adhesion molecule 1 (ICAM-1) is believed to be involved in metastasis of hepatocellular carcinoma (HCC) cells. Cancer stem cells promote tumor relapse and metastasis. We investigated whether ICAM-1 is a marker of HCC stem cells.
  
  
  METHODS
  Sphere formation and tumor formation assays were performed to investigate the stem cell properties of ICAM-1(+) cells in vitro and in vivo. A specific targeting system that inhibits ICAM-1 expression and hepatitis B virus transgenic mice (M-TgHBV) were used to investigate whether inhibition of ICAM-1 reduced tumor incidence and metastasis in vivo. We used real-time polymerase chain reaction and immunoblot analysis to assess ICAM-1 and Nanog expression in tumor cell lines, and flow cytometry analysis was used to investigate ICAM-1 expression in HCC and blood samples.
  
  
  RESULTS
  ICAM-1 was expressed on a minor cell population in HCC tumor cell lines, as well as in tumor tissues and circulating tumor cells isolated from patients and transgenic mice. ICAM-1(+) tumor cells had greater sphere-forming and tumorigenic capacities and increased expression of stemness-related genes compared with ICAM-1(-) tumor cells. The specific inhibition of ICAM-1 reduced formation and metastasis in M-TgHBV mice. ICAM-1 was found to be a marker of circulating tumor cells from patients and M-TgHBV mice. Increased numbers of CD45(-)ICAM-1(+) cells in blood samples of patients with HCC correlated with worse clinical outcomes. The stem cell transcription factor Nanog regulated expression of ICAM-1 in HCC stem cells.
  
  
  CONCLUSIONS
  ICAM-1 is a marker of HCC stem cells in humans and mice; ICAM-1 inhibitors slow tumor formation and metastasis in mice. ICAM-1 expression is regulated by the stem cell transcription factor Nanog.
authors: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Shupeng
authors: S
authors: Liu
authors: Nan
authors: N
authors: Li
authors: Xiya
authors: X
authors: Yu
authors: Xiao
authors: X
authors: Xiao
authors: Kai
authors: K
authors: Cheng
authors: Jingjing
authors: J
authors: Hu
authors: Jiaqi
authors: J
authors: Wang
authors: Dandan
authors: D
authors: Zhang
authors: Shuqun
authors: S
authors: Cheng
authors: Shanrong
authors: S
authors: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D018799:Intercellular Adhesion Molecule-1