Tamoxifen inhibition of ocular melanoma cell attachment to matrix proteins.
Tamoxifen plays a major role in the management of breast cancer in women and is currently used to a lesser extent in other neoplasias. Many of the pharmacological properties of tamoxifen are consistent with anti-estrogen activity, but it also has significant, although lesser, benefit in patients whose tumours are estrogen-receptor negative. We recently reported that murine B16 melanoma cell attachment to extracellular matrix proteins can be inhibited by calmodulin antagonists. In seeking a calmodulin antagonist that could be used clinically, we investigated tamoxifen, which is known to have calmodulin antagonist activity in vitro, and confirmed that it will inhibit murine melanoma cell attachment in vitro. In the current study, we examined the effect of tamoxifen on the attachment of human ocular melanoma cell lines to a range of extracellular matrix substrates to evaluate the potential relevance of calmodulin antagonists, including tamoxifen, to reducing metastatic spread of these tumours. We report that six ocular melanoma cell lines established from choroidal melanoma tumours showed rapid attachment to a range of substrates and that this attachment can be significantly reduced by an experimental calmodulin antagonist (J8) and by tamoxifen. In summary, we conclude that the ability of calmodulin antagonists, including tamoxifen, to inhibit ocular melanoma cell attachment to matrix proteins in vitro merits further investigation as it may offer another approach to reducing metastatic spread of these tumours.
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, U.K.
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MacNeil
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Wagner
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Rennie
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D010857:Pigment Epithelium of Eye / Q000166:cytology; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000473:pathology*
D016326:Extracellular Matrix Proteins; D013629:Tamoxifen