title: G protein-coupled receptor 87 (GPR87) promotes the growth and metastasis of CD133⁺ cancer stem-like cells in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a prevalent disease worldwide, and the majority of HCC-related deaths occur due to local invasion and distant metastasis. Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have been hypothesized to be responsible for metastatic disease. Recently, we and others have identified a CSC population from human HCC cell lines and xenograft tumors characterized by their expression of CD133. However, the precise molecular mechanisms by which CD133(+) cancer stem-like cells mediate HCC metastasis have not been sufficiently analyzed. Here, we have sorted HCC cells using CD133 as a cancer stem cell (CSC) marker by magnetic-activated cell sorting (MACS) and demonstrated that the CD133(+) HCC cells not only possess greater migratory and invasive capacity in vitro but are also endowed with enhanced metastatic capacity in vivo and in human HCC specimens when compared to CD133(-) HCC cells. Gene expression analysis of the CD133(+) and CD133(-) cells of the HCC line SMMC-7721 revealed that G protein-coupled receptor 87 (GPR87) is highly expressed in CD133(+) HCC cells. In this study, we explored the role of GPR87 in the regulation of CD133 expression. We demonstrated that the overexpression of GPR87 up-regulated CD133 expression, promoted CSC-associated migratory and invasive properties in vitro, and increased tumor initiation in vivo. Conversely, silencing of GPR87 expression reduced the levels of CD133 expression.
  
  
  CONCLUSIONS
  GPR87 promotes the growth and metastasis of CD133(+) cancer stem-like cells, and our findings may reveal new targets for HCC prevention or therapy.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Zhu
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhao
authors.forename: Lixing
authors.initials: L
authors.lastname: Zhang
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Guoping
authors.initials: G
authors.lastname: Jiang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000276:immunology*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D016133:Polymerase Chain Reaction; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D017931:DNA Primers; C526276:GPR87 protein, human; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D049368:Receptors, Lysophosphatidic Acid