Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors

Abstract

Background: Glioblastoma is the most aggressive and deadly brain tumor, with low disease-free period even after surgery and combined radio and chemotherapies. Among the factors contributing to the devastating effect of this tumor in the brain are the elevated proliferation and invasion rate, and the ability to induce a local immunosuppressive environment. The intermediateconductance Ca2+-activated K+ channel KCa3.1 is expressed in glioblastoma cells and in tumorinfiltrating cells.

Methods: We first describe the researches related to the role of KCa3.1 channels in the invasion of brain tumor cells and the regulation of cell cycle. In the second part we review the involvement of KCa3.1 channel in tumor-associated microglia cell behaviour.

Results: In tumor cells, the functional expression of KCa3.1 channels is important to substain cell invasion and proliferation. In tumor infiltrating cells, KCa3.1 channel activity is required to regulate their activation state. Interfering with KCa3.1 activity can be an adjuvant therapeutic approach in addition to classic chemotherapy and radiotherapy, to counteract tumor growth and prolong patient's survival.

Conclusion: In this mini-review we discuss the evidence of the functional roles of KCa3.1 channels in glioblastoma biology.

Keywords: 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34); Glioblastoma Multiforme (GBM); Intermediate conductance Ca2+-activated K+ channel (KCa3.1); brain tumors; invasion; microglia; proliferation..

Fig. (1)

A schematic representation of tumor microenvironment composed by glioma cells and tumor-associated microglia/macrophages (TAMs) is reported on the left, with high level of tumor growth and invasion and TAMs oriented toward a pro-tumor phenotype. Right: effect of KCa3.1 channel silencing/inhibition, with a reduction of tumor growth and invasion, and TAMs acquiring an anti-tumor phenotype.