Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity.
The possible association of intracellular Ca2+with metastasis in human cancer cells is poorly understood. We have studied Ca2+signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca2+was measured using a membrane-permeant fluorescent Ca2+-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca2+oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively). In contrast, no such oscillations were observed in weakly/non metastatic LNCaP and MCF-7 cells, although a rise in the resting Ca2+level could be induced by applying a high-K+solution. Various parameters of the oscillations depended on extracellular Ca2+and voltage-gated Na+channel activity. Treatment with either tetrodotoxin (a general blocker of voltage-gated Na+channels) or ranolazine (a blocker of the persistent component of the channel current) suppressed the Ca2+oscillations. It is concluded that the functional voltage-gated Na+channel expression in strongly metastatic cancer cells makes a significant contribution to generation of oscillatory intracellular Ca2+activity. Possible mechanisms and consequences of the Ca2+oscillations are discussed.
Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. nrizaner@ciu.edu.tr.|Biotechnology Research Centre, Cyprus International University, Haspolat, Mersin, Turkey. nrizaner@ciu.edu.tr.
Nahit
http://orcid.org/0000-0003-0274-5076
N
Rizaner
Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.|Biotechnology Research Centre, Cyprus International University, Haspolat, Mersin, Turkey.
Rustem
R
Onkal
Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Scott P
SP
Fraser
Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Alessandro
A
Pristerá
Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Kenji
K
Okuse
Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.|Biotechnology Research Centre, Cyprus International University, Haspolat, Mersin, Turkey.
Mustafa B A
MB
Djamgoz
D001943:Breast Neoplasms / Q000473:pathology*; D020013:Calcium Signaling; D005110:Extracellular Space / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D061986:MCF-7 Cells; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000473:pathology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
D061566:Voltage-Gated Sodium Channels
Calcium oscillation; Metastasis; Persistent current; Ranolazine; Tetrodotoxin; Voltage-gated sodium channel
Oncotarget. 2014 Jun 15;5(11):3455-71
24797725
Mol Cancer. 2014 Dec 11;13:264
25496128
Nature. 1998 Apr 30;392(6679):933-6
9582075
Nature. 1998 Oct 15;395(6703):645-8
9790183
Neurosci Lett. 2013 Oct 11;553:78-83
23973304
Clin Cancer Res. 2005 Aug 1;11(15):5381-9
16061851
J Cell Biol. 2014 Nov 24;207 (4):535-48
25404747
Oncogene. 2009 Apr 16;28(15):1792-806
19270724
Biophys J. 1977 Oct;20(1):79-111
901903
J Biol Chem. 2014 Sep 12;289(37):25418-30
25059669
J Natl Cancer Inst. 2010 Jul 21;102(14):1052-68
20554944
Oncotarget. 2015 Oct 20;6(32):32914-29
26452220
J Cell Sci. 2013 Nov 1;126(Pt 21):4939-49
23986482
J Pharmacol Exp Ther. 2006 Jul;318(1):214-22
16565163
FEBS Lett. 1995 Aug 7;369(2-3):290-4
7649275
Am J Physiol Cell Physiol. 2007 Oct;293(4):C1239-51
17634415
Cancer Res. 2010 Sep 1;70(17):6957-67
20651255
J Physiol. 1999 May 15;517 ( Pt 1):95-107
10226152
J Physiol. 1992;453:219-31
1334512
Oncogene. 2007 Nov 15;26(52):7380-5
17533368
Ann N Y Acad Sci. 1974;238:420-35
4613241
Int J Biochem Cell Biol. 2006 Mar;38(3):366-75
16300989
Cell Physiol Biochem. 2011;28(5):813-22
22178934
Neuron. 1996 Aug;17(2):275-85
8780651
J Cell Physiol. 2011 Feb;226(2):456-68
20717964
Science. 1998 Jan 9;279(5348):227-30
9422695
Am J Pathol. 1997 Apr;150(4):1213-21
9094978
J Physiol. 1992 Mar;448:53-72
1317444
Biochim Biophys Acta. 2015 Aug;1853(8):1772-82
25937071
Life Sci. 2010 Nov 20;87(19-22):587-95
20875431
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2011-6
18250319
Prostate. 2001 Aug 1;48(3):165-78
11494332
Pflugers Arch. 2014 Oct;466(10 ):1921-32
24458591
Compr Physiol. 2013 Jan;3(1):221-42
23720286
Eur Biophys J. 2004 May;33(3):180-93
14963621
Cancer Lett. 2012 Oct 1;323(1):58-61
22484465
Eur J Pharmacol. 2003 Jun 27;471(3):157-64
12826234
J Neurochem. 2009 Nov;111(3):745-56
19719824
Recent Pat Anticancer Drug Discov. 2013 Jan 1;8(1):66-84
23116083
Asian J Androl. 2009 Mar;11(2):157-65
19234481
J Cell Physiol. 2007 Feb;210(2):469-78
17051596
Biochim Biophys Acta. 2014 Mar;1840(3):964-9
24269537
Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
12838335
Oncol Rep. 2010 May;23(5):1293-9
20372843
Biochim Biophys Acta. 2015 Oct;1848(10 Pt B):2502-11
25150047
Philos Trans R Soc Lond B Biol Sci. 2014 Feb 03;369(1638):20130097
24493745
Springerplus. 2013 Dec;2(1):54
23450760
Annu Rev Physiol. 1996;58:349-62
8815799
Oncotarget. 2015 Jul 10;6(19):17221-36
25980497
Recent Pat Anticancer Drug Discov. 2007 Nov;2(3):189-202
18221062
Exp Cell Res. 2009 Jul 15;315(12):2072-80
19285978
Breast Cancer Res Treat. 2007 Dec;106(2):151-60
17260093
Am J Physiol Cell Physiol. 2014 Mar 15;306(6):C515-26
24225884
Biochim Biophys Acta. 2003 Oct 13;1616(2):107-11
14561467
Curr Pharm Des. 2006;12(28):3681-95
17073667
Int J Biochem Cell Biol. 2007;39(4):774-86
17307016
Br J Pharmacol. 2016 Jan;173(1):177-90
26454020
Cancer Cell Int. 2009 Aug 18;9:23
19689790
Prostate. 2001 Mar 1;46(4):262-74
11241548
J Neurochem. 2004 May;89(3):739-49
15086530
Oncol Rep. 2013 May;29(5):1835-40
23427012
Physiol Rev. 1999 Jul;79(3):763-854
10390518
J Biol Chem. 1985 Dec 5;260(28):14998-507
2933397
Oncotarget. 2015 Oct 27;6(33):34831-45
26498680
Biomed Res Int. 2015;2015:409245
25977921
J Gen Physiol. 1989 Aug;94(2):329-48
2794968