title: Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway.
abstract: OBJECTIVE
  Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction.
  
  
  METHODS
  Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion.
  
  
  RESULTS
  Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200× microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition.
  
  
  CONCLUSIONS
  TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Li-Yi
authors.initials: LY
authors.lastname: Zhang
authors.forename: Sui-Sui
authors.initials: SS
authors.lastname: Dong
authors.forename: Lu-Hui
authors.initials: LH
authors.lastname: Lu
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Dai
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Kar Lok
authors.initials: KL
authors.lastname: Kong
authors.forename: Dora L
authors.initials: DL
authors.lastname: Kwong
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D006224:Cricetinae; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051154:Wnt2 Protein / Q000378:metabolism* / Q000502:physiology
chemical_list: D051154:Wnt2 Protein