Changes in the motility of B16F10 melanoma cells induced by alterations in resting calcium influx.
Alterations in the extracellular Ca(2+) or K(+) concentration had significant influences on the motility of B16F10 melanoma cells measured in the absence of exogenous integrins using a conventional Boyden chamber assay. At normal K(+) concentrations, motility increased slightly when the concentration of Ca(2+) was increased 10-fold. At normal Ca(2+) concentrations, motility increased by 290% when the extracellular K(+) concentration was reduced 10-fold (from control of 5.4 mM to 0.54 mM), and increased to 250% of control levels when the K(+) concentration was increased between 30 and 54 mM, but was relatively uninfluenced at K(+) concentrations between 5 and 30 mM. Simultaneous application of low concentrations (20 microM) of GdCl(3) completely prevented the effects of low and high K(+) on motility. Exposure to Gd(3+) or Tb(3+) also produced a flattening of the cells and enhanced cell attachment. Although the steady state intracellular Ca(2+) concentration was not significantly influenced by the K(+) concentration, the resting permeability to divalent cations, determined from Mn(2+) quench rates in fura-loaded cells, was significantly increased by a reduction in the K(+) concentration. These results indicate that resting Ca(2+) influx is critical to the movement of B16F10 melanoma cells, and demonstrate that lanthanides, which block resting Ca(2+) influx pathways, are potent antimotility agents.
Department of Biochemistry, Kirksville Cellege Osteopathic Medicine, Kirksville, MO 63501, USA. jcox@kcom.edu
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Cox
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Lancaster
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Carlson
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D017895:Manganese Compounds / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D011188:Potassium / Q000494:pharmacology; D013725:Terbium / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology
D002121:Calcium Channel Blockers; D002712:Chlorides; D017895:Manganese Compounds; D013725:Terbium; D016222:Fibroblast Growth Factor 2; D003035:Cobalt; D015759:Ionomycin; C067490:terbium chloride; D005682:Gadolinium; C018021:cobaltous chloride; C038958:gadolinium chloride; C025340:manganese chloride; D011188:Potassium; D002118:Calcium