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

Abstract

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.

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

“…The data suggests that DNA methylation is responsible for the observed decrease of Kv1.3 gene expression [22]. A significantly reduced expression of the channels was also observed in kidney, bladder, pancreas, lung, brain (astrocytoma, oligodendroglioma, and glioblastoma), stomach and prostate cancer [8,18,[22][23][24]. In the case of prostate cancer, there is also an inverse correlation between the expression of the channels and the stage of the disease [23].…”

“…An increased expression of Kv1.3 channels was observed in the case of breast, colon, smooth muscle (leiomyosarcoma), skeletal muscle (alveolar rhabdomyosarcoma) and lymph node cancer [8,17] and in mature neoplastic B cells in chronic lymphocytic leukemia (B-CLL) [20]. A significantly increased expression of Kv1.3 channels that was positively correlated with tumor aggressiveness was recently observed in the case of leiomyosarcoma and alveolar rhabdomyosarcoma [8,18]. In the case of breast cancer, contradictory data has been obtained [17, 21, and 22].…”

“…Recently, Kv1.3 channels are considered a new, potentially attractive molecular target in both cancer diagnostics and therapy [6][7][8][17][18][19][20]. First of all, several studies have demonstrated altered expression of Kv1.3 in some cancer specimens in comparison with normal tissue [6-8, 17, 18].…”

Association between Genetic Variations in Kv7.5 and Susceptibility of Lung Cancer in a Northeast Chinese Population

“…The latest probable explanation is that non-conducting mechanism contribute to proliferation rather than ion-flux mechanism [24]. Previous studies manifested for the first time that Kv1.3 and Kv1.5 are altered during smooth muscle carcinogenesis and showed that the increased expression of K1.3 and Kv1.5 prompt leiomyosarcoma aggressiveness [25]. Likewise, the result of previous study demonstrated that the specific knockdown of Kv9.3 decrease proliferation in human colon and lung carcinoma cells [26].…”

The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer

“…Although Kv1.3 was first cloned from brain tissue, its expression is widely distributed throughout the body (Swanson et al, 1990; Bielanska et al, 2009, 2010). This channel is highly expressed in lymphocytes and the olfactory bulb (Stuhmer et al, 1989), and several studies have reported that it is also expressed in the hippocampus (Veh et al, 1995), epithelia (Grunnet et al, 2003), adipose tissue (Xu et al, 2004), and both skeletal, and smooth muscle (Villalonga et al, 2008; Bielanska et al, 2012a,b). …”