Overexpression of Large-Conductance Calcium-Activated Potassium Channels in Human Glioblastoma Stem-Like Cells and Their Role in Cell Migration.
Glioblastomas (GBMs) are brain tumors characterized by diffuse invasion of cancer cells into the healthy brain parenchyma, and establishment of secondary foci. GBM cells abundantly express large-conductance, calcium-activated potassium (BK) channels that are thought to promote cell invasion. Recent evidence suggests that the GBM high invasive potential mainly originates from a pool of stem-like cells, but the expression and function of BK channels in this cell subpopulation have not been studied. We investigated the expression of BK channels in GBM stem-like cells using electrophysiological and immunochemical techniques, and assessed their involvement in the migratory process of this important cell subpopulation. In U87-MG cells, BK channel expression and function were markedly upregulated by growth conditions that enriched the culture in GBM stem-like cells (U87-NS). Cytofluorimetric analysis further confirmed the appearance of a cell subpopulation that co-expressed high levels of BK channels and CD133, as well as other stem cell markers. A similar association was also found in cells derived from freshly resected GBM biopsies. Finally, transwell migration tests showed that U87-NS cells migration was much more sensitive to BK channel block than U87-MG cells. Our data show that BK channels are highly expressed in GBM stem-like cells, and participate to their high migratory activity. J. Cell. Physiol. 232: 2478-2488, 2017. © 2016 Wiley Periodicals, Inc.
Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University, Latina, Italy.
Paolo
P
Rosa
Department of Chemistry Biology and Biotechnology, University of Perugia, Perugia, Italy.
Luigi
L
Sforna
Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University, Latina, Italy.
Silvia
S
Carlomagno
Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University, Latina, Italy.
Giorgio
G
Mangino
Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University, Latina, Italy.
Massimo
M
Miscusi
Department of Experimental Medicine, University of Perugia, Perugia, Italy.|Department of Physiology and Biochemistry, University of Malta, Msida, Malta.
Mauro
M
Pessia
Department of Chemistry Biology and Biotechnology, University of Perugia, Perugia, Italy.
Fabio
F
Franciolini
Department of Medico-Surgical Sciences and Biotechnologies, "La Sapienza" University, Latina, Italy.
Antonella
A
Calogero
Department of Chemistry Biology and Biotechnology, University of Perugia, Perugia, Italy.
Luigi
L
Catacuzzeno
D000071916:AC133 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D061251:Primary Cell Culture; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; C000606023:PROM1 protein, human; D026902:Potassium Channel Blockers