MacNeil S, Wagner M, Rennie I G
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, U.K.
Pigment Cell Res. 1994 Aug;7(4):222-6. doi: 10.1111/j.1600-0749.1994.tb00053.x.
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.
他莫昔芬在女性乳腺癌治疗中发挥着重要作用，目前在其他肿瘤中的应用较少。他莫昔芬的许多药理特性与抗雌激素活性相符，但在肿瘤雌激素受体阴性的患者中也有显著益处，尽管程度稍低。我们最近报道，钙调蛋白拮抗剂可抑制小鼠B16黑色素瘤细胞与细胞外基质蛋白的附着。在寻找一种可用于临床的钙调蛋白拮抗剂时，我们研究了他莫昔芬，已知其在体外具有钙调蛋白拮抗剂活性，并证实它在体外可抑制小鼠黑色素瘤细胞的附着。在本研究中，我们检测了他莫昔芬对人眼黑色素瘤细胞系与一系列细胞外基质底物附着的影响，以评估包括他莫昔芬在内的钙调蛋白拮抗剂对减少这些肿瘤转移扩散的潜在相关性。我们报告，从脉络膜黑色素瘤肿瘤建立的六种眼黑色素瘤细胞系对一系列底物表现出快速附着，并且这种附着可被一种实验性钙调蛋白拮抗剂（J8）和他莫昔芬显著降低。总之，我们得出结论，包括他莫昔芬在内的钙调蛋白拮抗剂在体外抑制眼黑色素瘤细胞与基质蛋白附着的能力值得进一步研究，因为这可能为减少这些肿瘤的转移扩散提供另一种方法。
