title: Structure and function of the N-cadherin/catenin complex in retinoblastoma.
abstract: OBJECTIVE
  To identify in human retinoblastoma and normal retinal tissue the type of cadherin, its relationship with cytoplasmic catenins, and its participation in invasion.
  
  
  METHODS
  The cadherin/catenin complex was characterized in surgical retinoblastoma specimens from five patients and human retinas from four donor eyes by immunocytochemistry, flow cytometry, and coimmunoprecipitation with antibodies against N-cadherin, alpha-catenin, and beta-catenin, followed by Western blot analysis or autoradiography. Y79 and WERI-Rb-1 retinoblastoma cell lines serve the evaluation of the cadherin/catenin complex in aggregation and collagen type I invasion in vitro. The association of the cadherin/catenin complex with the cytoskeleton was examined by an antibody-capping assay.
  
  
  RESULTS
  In retinoblastoma and normal retina N-cadherin associated with alpha-catenin and beta-catenin but not E- or P-cadherin. The N-cadherin/catenin complex formed a regular, linear, and continuous honeycomb pattern in normal retina that was irregular, clustered, and interrupted in retinoblastoma. The N-cadherin/catenin complex was found also in the retinoblastoma cell lines WERI-Rb and Y79, in which it also showed an irregular pattern. Both cell lines were invasive in collagen type I, and invasion was inhibited by the GC-4 antibody, which functionally neutralizes N-cadherin. Less GC-4 antibody was needed to inhibit invasion of Y79 cells, which expressed N-cadherin at a lower level, than to inhibit invasion of WERI-Rb-1 cells. In both cell lines, antibody capping of the N-cadherin/catenin complex indicated that its linkage with the cytoskeleton were weak or absent.
  
  
  CONCLUSIONS
  Retinoblastoma cells, in contrast with normal retina, express an N-cadherin/catenin complex that is irregularly distributed and weakly linked to the cytoskeleton. In retinoblastoma, this complex acts as an invasion promoter.
authors.affiliation: Department of Ophthalmology, Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Van Aken
authors.forename: Peggy
authors.initials: P
authors.lastname: Papeleu
authors.forename: Patrick
authors.initials: P
authors.lastname: De Potter
authors.forename: Erik
authors.initials: E
authors.lastname: Bruyneel
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.forename: Stefan
authors.initials: S
authors.lastname: Seregard
authors.forename: Anders
authors.initials: A
authors.lastname: Kvanta
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: De Laey
authors.forename: Marc M
authors.initials: MM
authors.lastname: Mareel
mesh_terms: D001345:Autoradiography; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D011233:Precipitin Tests; D012160:Retina / Q000378:metabolism; D019572:Retinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014407:Tumor Cells, Cultured / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin