Abstract
AbstractPurpose To investigate the expression of HSP90 in human conjunctival melanoma (CM) cell lines and primary human melanocytes, and to assess the effects of HSP90 inhibitors on cell growth and proliferation.Methods CM cell lines (CRMM1 and 2; CM2005.1) and primary human melanocytes (n=3, P2 to P4) were immunolabelled for HSP90, and visualised using immunofluorescence and confocal microscopy. HSP90 expression was also examined in cell lysates from CM cell lines (CRMM1 and 2; CM2005.1) and primary melanocytes (n=3). The effect of several HSP90 inhibitors (17DMAG, SM252 and SM122) on cell growth and viability was assessed at 24hrs.Results CRMM1 and 2, and CM2005.1 cells showed strong cytoplasmic expression of HSP90, with low levels of cytoplasmic expression in primary melanocytes. This was confirmed using western blot. The HSP90 inhibitors induced dose‐dependent cell death in CM cells, 17DMAG (water soluble) being most effective (LD50 at 24 hrs ~30uM compared with ~50um for SM122 and SM122).Primary human melanocytes viability was not significantly reduced by the HSP90 inhibitors.Conclusion HSP90 is a widely expressed chaperone protein that can regulate cell growth, survival and angiogenesis pathways. CM cell lines expressed high levels of HSP90 protein compared to melanocytes, consistent with a recent study of primary conjunctival melanoma specimens, that found over‐expressed HSP90 in CM, particularly recurrent tumours. HSP90 inhibitors may be useful in inhibiting CM growth alone or in combination therapies. Funding: National Foundation for Medical Research & Innovation (MCM & RMC); Lions NSW Eyebank
Published Version
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