Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis.
Potassium channels, the most diverse superfamily of ion channels, have recently emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large conductance Ca(2+)-activated K(+) channels, often referred to as BK channels, are at the crossroads of several tumor-associated processes such as cell proliferation, survival, secretion and migration. Despite the high BK channel expression in osteosarcoma (OS), their function has not yet been investigated in this malignant bone pathology. Here, using stable RNA interference to reduce the expression of hSlo, the human pore-forming alpha-subunit of the BK channel, in human Cal72 OS cells, we show that BK channels play a functional role in carcinogenesis. Our results reveal for the first time that BK channels exhibit antitumoral properties in OS in vivo and affect the tumor microenvironment through the modulation of both chemokine expression and leukocyte infiltration.
Cambien
Béatrice
B
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
Rezzonico
Roger
R
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
Vitale
Sébastien
S
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
Rouzaire-Dubois
Béatrice
B
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR 9040, Gif-sur-Yvette, France.
Dubois
Jean-Marc
JM
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR 9040, Gif-sur-Yvette, France.
Barthel
Robert
R
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
Soilihi
Babou Karimdjee
BK
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.|CHU, Hôpital de l'Archet II, Service de Chirurgie Générale et Cancérologie Digestive, Nice F-06202, France.
Mograbi
Baharia
B
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM ERI 21, Nice F-06107, France.
Schmid-Alliana
Annie
A
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
Schmid-Antomarchi
Heidy
H
Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.|INSERM, U638, Nice F-06107, France.
D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D034741:RNA, Small Interfering