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1 From the Departments of Ophthalmology and 4 Clinical Chemistry, Microbiology, and Immunology and the 2 Laboratory of Experimental Cancerology, Ghent University Hospital, Gent, Belgium; the 3 Ocular Oncology Unit, Cliniques Universitaires St-Luc, Brussels, Belgium; and the 5 Ophthalmic Pathology and Oncology Service, St. Erik’s Eye Hospital, Stockholm, Sweden.
PURPOSE. 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, 
-catenin,
and ß-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
-catenin and ß-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.
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