TAMOXIFEN INHIBITION OF OCULAR MELANOMA CELL ATTACHMENT TO MATRIX PROTEINS

Tamoxifen plays a major role in the management of breast cancer in wom en and is currently used to a lesser extent in other neoplasias. Many of the pharmacological properties of tamoxifen are consistent with ant i-estrogen activity, but it also has significant, although lesser, ben efit in patients whose tumours are estrogen-receptor negative. We rece ntly reported that murine B16 melanoma cell attachment to extracellula r matrix proteins can be inhibited by calmodulin antagonists. In seeki ng a calmodulin antagonist that could be used clinically, we investiga ted tamoxifen, which is known to have calmodulin antagonist activity i n vitro, and confirmed that it will inhibit murine melanoma noma cell attachment in vitro. In the current study, we examined the effect of t amoxifen on the attachment of human ocular melanoma cell lines to a ra nge of extracellular matrix substrates to evaluate the potential relev ance of calmodulin antagonists, including tamoxifen, to reducing metas tatic spread of these tumours. We report that six ocular melanoma cell lines established from choroidal melanoma tumours showed rapid attach ment to a range of substrates and that this attachment can be signific antly reduced by an experimental calmodulin antagonist (J8) and by tam oxifen. In summary, we conclude that the ability of calmodulin antagon ists, including tamoxifen, to inhibit ocular melanoma cell attachment to matrix proteins in vitro merits further investigation as it may off er another approach to reducing metastatic spread of these tumours.