title: Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma.
abstract: BACKGROUND
  As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection.
  
  
  METHODS
  We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed.
  
  
  RESULTS
  Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P < 0.001). Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein.
  
  
  CONCLUSIONS
  The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. The measurement of soluble CD147 may offer a useful approach in diagnosis of HCC.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Hao
authors.forename: You-Xu
authors.initials: YX
authors.lastname: Zhao
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Xiu-Xuan
authors.initials: XX
authors.lastname: Sun
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Nan
authors.affiliation: Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China. znchen@fmmu.edu.cn.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.forename: Huijie
authors.initials: H
authors.lastname: Bian
mesh_terms: D000328:Adult; D000368:Aged; D051926:Basigin / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012372:ROC Curve; D015398:Signal Transduction; D012995:Solubility; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D000509:alpha-Fetoproteins; D051926:Basigin; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2