Yoshinaga I G, Dekker S K, Mihm M C, Byers H R
Department of Dermatology, Boston University Medical Center, MA 02118-2515.
Melanoma Res. 1994 Dec;4(6):371-8. doi: 10.1097/00008390-199412000-00005.
We characterized the effects of extracellular Mg2+ and Ca2+ on the regulation of integrin-mediated cell migration of melanoma cells on type IV collagen and fibronectin. Melanoma cell motility was studied using transmembrane migration in modified Boyden chambers and time-lapse video image analysis. Increasing Mg2+ or Ca2+ ion concentration from 0.1 to 10 mM produces distinct effects on melanoma cell migration on type IV collagen. Increasing Mg2+ ion concentration increased cell migration to a maximum at 5 mM, followed by a decrease at 10 mM. In contrast, Ca2+ alone did not support cell migration on this substrate. Combinations of both cations indicate that Ca2+ decreases cell migration in the presence of Mg2+. However, as opposed to the findings on collagen, peak migration on fibronectin was observed at 1 mM and Ca2+ alone was able to support migration on fibronectin. The Mg(2+)-enhanced migration was inhibited by function-blocking monoclonal antibodies anti-alpha 2 or anti-beta 1 integrin subunit on the type IV collagen and anti-alpha 5 and anti-beta 1 on fibronectin. Taken together, the data indicate that Mg2+ promotes the integrin-mediated cell migration, whereas Ca2+ has the opposite effect. The Ca2+ and Mg2+ concentration in the tumour extracellular microenvironment may modulate integrin-mediated functions and melanoma metastasis.
我们研究了细胞外镁离子（Mg2+）和钙离子（Ca2+）对黑色素瘤细胞在IV型胶原和纤连蛋白上整合素介导的细胞迁移调节的影响。使用改良的博伊登小室中的跨膜迁移和延时视频图像分析来研究黑色素瘤细胞的运动性。将Mg2+或Ca2+离子浓度从0.1 mM增加到10 mM，对黑色素瘤细胞在IV型胶原上的迁移产生不同影响。增加Mg2+离子浓度会使细胞迁移在5 mM时达到最大值，随后在10 mM时下降。相比之下，单独的Ca2+不支持细胞在该基质上迁移。两种阳离子的组合表明，在存在Mg2+的情况下，Ca2+会降低细胞迁移。然而，与在胶原上的发现相反，在纤连蛋白上观察到在1 mM时迁移达到峰值，并且单独的Ca2+能够支持在纤连蛋白上的迁移。在IV型胶原上，Mg(2+)增强的迁移被抗α2或抗β1整合素亚基的功能阻断单克隆抗体抑制，在纤连蛋白上则被抗α5和抗β1抑制。综上所述，数据表明Mg2+促进整合素介导的细胞迁移，而Ca2+则具有相反的作用。肿瘤细胞外微环境中的Ca2+和Mg2+浓度可能调节整合素介导的功能和黑色素瘤转移。
