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Elisabeth H. Van Aken, Peggy Papeleu, Patrick De Potter, Erik Bruyneel, Jan Philippé, Stefan Seregard, Anders Kvanta, Jean-Jacques De Laey, Marc M. Mareel; Structure and Function of the N-Cadherin/Catenin Complex in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2002;43(3):595-602.
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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, α-catenin,
and β-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 withα
-catenin and β-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
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