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.
Yoshinaga
I G
IG
Department of Dermatology, Boston University Medical Center, MA 02118-2515.
Dekker
S K
SK
Mihm
M C
MC
Byers
H R
HR
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D003094:Collagen; D008274:Magnesium; D002118:Calcium