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J Choi, BY J T Yue, AM Miller, PA Knepper; Influence of sCD44 on the Expression of erbB2, a Cell Survival Pathway, and Rescue of Bovine Trabecular Meshwork Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4081.
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Purpose: The CD44 transmembrane receptor is implicated in cell growth and survival. Increased concentrations of the ectodomain of CD44, soluble CD44 (sCD44) are present in the aqueous humor of patients with primary open-angle glaucoma. We tested the effects of exogenous sCD44 on cell viability and cell expression of erbB2 in bovine trabecular meshwork (TM) cells and rescue of TM cells from the cytotoxicity of sCD44 by epidermal growth factor (EGF) and 17-alpha-methyl-testosterone. Methods: TM cells were grown in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal calf serum (FCS) until confluent. The cells were washed twice with PBS, and incubated in DMEM containing 0.1% FCS with 10 ng/ml purified sCD44, 17-alpha-methyl-testosterone, EGF, or PBS for 12, 24, and 48 hours. Western analysis was performed using antibodies specific for erbB2, erbB2 phosphorylated, erbB3, CD44, and MMP-9. Dual-labeling immunofluorescence was used to localize erbB2, erbB3, and CD44. Results: CD44 associates with erbB2 and erbB3 as determined by immunofluorescence microscopy, immunoprecipitation, and Western blotting. sCD44 significantly reduced cell viability, membrane CD44, erbB2 phosphorylation, erbB2-erbB3 heterodimerization, and increased MMP-9. Significantly less cell death occurred in TM cells with co-administration of sCD44 and 17-alpha-methyl-testosterone. Conclusions: Membrane CD44 functions in TM cells through the cell survival pathway of erbB2. sCD44 disrupts membrane CD44 signaling with erbB2-erbB3. TM cells were rescued from the cytotoxic effects of sCD44 by addition of 17-alpha-methyl-testosterone.
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