Differential effect of magnesium and calcium on integrin-mediated melanoma cell migration on type IV collagen and fibronectin.

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.