title: Claudin-11 decreases the invasiveness of bladder cancer cells.
abstract: The expression of claudin-11 in benign and malignant bladder tissue and the effect of forced expression of claudin-11 on tight junction function and invasiveness of bladder cancer cells were studied. Claudin-11 expression was tested in bladder cancer cell lines (T24/83, RT 112/84 and EJ138) using reverse transcription-polymerase chain reaction (RT-PCR) and in benign and malignant bladder tissue by quantitative RT-PCR and immunohistochemistry. T24/83 cells were transfected with the pcDNA.1/NT-GFP-TOPO vector containing full-length human claudin-11 sequence. Stable-transfected cells overexpressing claudin-11 (T24Cl-11Ex), wild-type cells (T24WT) and the empty plasmid control clone (T24GFP) were compared using transurothelial resistance (TUR), in vitro adhesion, invasion and growth assays. Claudin-11 was strongly expressed in the non-invasive RT112/84 cell line compared to the invasive T24/83 and EJ138 TCC cell lines. Benign bladder tissue demonstrated equal expression of claudin-11 mRNA as carcinoma, but displayed more intense staining than malignant tissue on immunohistochemistry. Forced-expression of claudin-11 in T24/83 cells was confirmed by PCR, immunoprecipitation and by immunofluorescence, which demonstrated increased perinuclear claudin-11 staining. Forced expression of claudin-11 did not affect TUR (p = 0.243), but significantly reduced invasion (p = 0.001) while increasing cell matrix adhesion (p = 0.001) and growth rates (p = 0.001). The greater expression of claudin-11 in benign vs. malignant tissue and non-invasive vs. invasive cell lines, and its effect in reducing bladder cancer cell invasiveness suggests that claudin-11 may have a role in preventing cancer progression and may serve as a therapeutic target in reducing metastasis.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Ninaad S
authors.initials: NS
authors.lastname: Awsare
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.forename: Mark D
authors.initials: MD
authors.lastname: Haynes
authors.forename: Philip N
authors.initials: PN
authors.lastname: Matthews
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057167:Claudins; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C120453:CLDN11 protein, human; D057167:Claudins; D009419:Nerve Tissue Proteins