Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness

Bielanska,Joanna; Hernández-Losa,Javier; Moline,Teresa; Somoza,Rosa; Ramón y Cajal,Santiago; Condom,Enric; Ferreres,Joan   Carles; Felipe,Antonio

doi:10.3892/ol.2012.718

Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness

Authors:
- Joanna Bielanska
- Javier Hernández-Losa
- Teresa Moline
- Rosa Somoza
- Santiago Ramón y Cajal
- Enric Condom
- Joan Carles Ferreres
- Antonio Felipe
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Affiliations: Molecular Physiology Laboratory, Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, E-08028 Barcelona, Spain, Department of Pathology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, E-08035 Barcelona, Spain , Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, E-08907 Barcelona, Spain
Published online on: May 16, 2012 https://doi.org/10.3892/ol.2012.718
Pages: 227-230

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Abstract

Voltage-dependent K+ channels (Kv) are involved in the proliferation and differentiation of mammalian cells, since Kv antagonists impair cell cycle progression. Although myofibers are terminally differentiated, some myoblasts may re-enter the cell cycle and proliferate. Since Kv1.3 and Kv1.5 expression is remodeled during tumorigenesis and is involved in smooth muscle proliferation, the purpose of this study was to analyze the expression of Kv1.3 and Kv1.5 in smooth muscle neoplasms. In the present study, we examined human samples of smooth muscle tumors together with healthy specimens. Thus, leiomyoma (LM) and leiomyosarcoma (LMS) tumors were analyzed. Results showed that Kv1.3 was poorly expressed in the healthy muscle and indolent LM specimens, whereas aggressive LMS showed high levels of Kv1.3 expression. Kv1.5 staining was correlated with malignancy. The findings show a remodeling of Kv1.3 and Kv1.5 in human smooth muscle sarcoma. A correlation of Kv1.3 and Kv1.5 expression with tumor aggressiveness was observed. Thus, our results indicate Kv1.5 and Kv1.3 as potential tumorigenic targets for aggressive human LMS.

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1	Hille B: Ion Channels of Excitable Membranes. 3rd edition. Sinauer; Sunderland, MA: xviii. pp. 8142001
2	Cidad P, Moreno-Dominguez A, Novensa L, et al: Characterization of ion channels involved in the proliferative response of femoral artery smooth muscle cells. Arterioscler Thromb Vasc Biol. 30:1203–1211. 2010. View Article : Google Scholar : PubMed/NCBI
3	Cheong A, Li J, Sukumar P, et al: Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers. Cardiovasc Res. 89:282–289. 2011. View Article : Google Scholar : PubMed/NCBI
4	Conti M: Targeting K⁺ channels for cancer therapy. J Exp Ther Oncol. 4:161–166. 2004.
5	Felipe A, Vicente R, Villalonga N, et al: Potassium channels: new targets in cancer therapy. Cancer Detect Prev. 30:375–385. 2006. View Article : Google Scholar : PubMed/NCBI
6	Kunzelmann K: Ion channels and cancer. J Membr Biol. 205:159–173. 2005. View Article : Google Scholar
7	Pardo LA: Voltage-gated potassium channels in cell proliferation. Physiology (Bethesda). 19:285–292. 2004. View Article : Google Scholar : PubMed/NCBI
8	Wonderlin WF and Strobl JS: Potassium channels, proliferation and G1 progression. J Membr Biol. 154:91–107. 1996. View Article : Google Scholar : PubMed/NCBI
9	Felipe A, Bielanska J, Comes N, et al: Targeting the voltage-dependent K⁺ channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention. Curr Med Chem. 9:661–674. 2011.
10	Vicente R, Escalada A, Villalonga N, et al: Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K⁺ channel in macrophages. J Biol Chem. 281:37675–37685. 2006. View Article : Google Scholar
11	Villalonga N, Martinez-Marmol R, Roura-Ferrer M, et al: Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation. Biochim Biophys Acta. 1783:728–736. 2008. View Article : Google Scholar
12	Swanson R, Marshall J, Smith JS, et al: Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron. 4:929–939. 1990. View Article : Google Scholar : PubMed/NCBI
13	Bielanska J, Hernandez-Losa J, Perez-Verdaguer M, et al: Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human cancer. Curr Cancer Drug Targets. 9:904–914. 2009. View Article : Google Scholar
14	Vicente R, Escalada A, Coma M, et al: Differential voltage-dependent K⁺ channel responses during proliferation and activation in macrophages. J Biol Chem. 278:46307–46320. 2003.PubMed/NCBI
15	Villalonga N, Escalada A, Vicente R, et al: Kv1.3/Kv1.5 heteromeric channels compromise pharmacological responses in macrophages. Biochem Biophys Res Commun. 352:913–918. 2007. View Article : Google Scholar : PubMed/NCBI
16	Bielanska J, Hernandez-Losa J, Moline T, et al: Differential expression of Kv1.3 and Kv1.5 voltage-dependent K⁺ channels in human skeletal muscle sarcomas. Cancer Invest. 30:203–208. 2012. View Article : Google Scholar
17	Bielanska J, Hernandez-Losa J, Moline T, et al: Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human fetus. Cell Physiol Biochem. 26:219–226. 2010. View Article : Google Scholar
18	Lan M, Shi Y, Han Z, et al: Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells. Cancer Biol Ther. 4:1342–1347. 2005. View Article : Google Scholar : PubMed/NCBI
19	Castellvi J, Garcia A, Ruiz-Marcellan C, et al: Cell signaling in endometrial carcinoma: phosphorylated 4E-binding protein-1 expression in endometrial cancer correlates with aggressive tumors and prognosis. Hum Pathol. 40:1418–1426. 2009. View Article : Google Scholar : PubMed/NCBI
20	Archer SL, Souil E, Dinh-Xuan AT, et al: Molecular identification of the role of voltage-gated K⁺ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J Clin Invest. 101:2319–2330. 1998.PubMed/NCBI
21	Chen TT, Luykenaar KD, Walsh EJ, Walsh MP and Cole WC: Key role of Kv1 channels in vasoregulation. Circ Res. 99:53–60. 2006. View Article : Google Scholar : PubMed/NCBI
22	Nelson MT and Quayle JM: Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 268:C799–C822. 1995.PubMed/NCBI