engleski

Resting potential of cancer stem cells

There is a functional relationship between resting membrane potential (Vm) and cell proliferation and differentiation, which can be seen in many cells including normal stem cells and various tumors. Sundelacruz et al have shown that Vm depolarization promotes maintenance of mesenchymal stem cells in an undifferentiated stage (1). We postulated that depolarized Vm may also help maintain a population of cancer stem cells (CSCs), undifferentiated subpopulation of cancer responsible for tumor formation, relapse and metastasis. Therefore, Vm was measured by Nystatin-perforated patch technique in HMLE cells overexpressing Twist (HMLEtwist), a model for cancer stem cells (2). Also, we measured Vm of SUM159 and MCF7, two breast cancer cell lines with high and low percentage of CSCs among whole population, respectively. We show that SUM159 cells are more depolarized than MCF7. Regarding breast CSC model, there was no difference in Vm between HMLEtwist and control HMLE cells, pointing to potential limitations of this model. Furthermore, we used proprietary potassium ionophores (3) to modulate Vm in CSC model. Compound 613 caused depolarization in HMLEtwist estimated by using the cationic dye DioC6(3). Preliminary electrophysiological measurements indicate that the compound at first hyperpolarizes cells, which is followed by depolarization. Measurements of resting potential in CSCs with and without modulators will be further continued. Moreover, we will relate Vm values to expression of various ion channels.

Breast cancer stem cells ; Membrane potential ; Potassium Ionophores

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