PMID- 20392929
OWN - NLM
STAT- MEDLINE
DCOM- 20100713
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 299
IP  - 1
DP  - 2010 Jul
TI  - CXCL12-induced glioblastoma cell migration requires intermediate conductance 
      Ca2+-activated K+ channel activity.
PG  - C175-84
LID - 10.1152/ajpcell.00344.2009 [doi]
AB  - The activation of ion channels is crucial during cell movement, including 
      glioblastoma cell invasion in the brain parenchyma. In this context, we describe 
      for the first time the contribution of intermediate conductance Ca(2+)-activated 
      K (IK(Ca)) channel activity in the chemotactic response of human glioblastoma 
      cell lines, primary cultures, and freshly dissociated tissues to CXC chemokine 
      ligand 12 (CXCL12), a chemokine whose expression in glioblastoma has been 
      correlated with its invasive capacity. We show that blockade of the IK(Ca) 
      channel with its specific inhibitor 1-[(2-chlorophenyl) 
      diphenylmethyl]-1H-pyrazole (TRAM-34) or IK(Ca) channel silencing by short 
      hairpin RNA (shRNA) completely abolished CXCL12-induced cell migration. We 
      further demonstrate that this is not a general mechanism in glioblastoma cell 
      migration since epidermal growth factor (EGF), which also activates IK(Ca) 
      channels in the glioblastoma-derived cell line GL15, stimulate cell chemotaxis 
      even if the IK(Ca) channels have been blocked or silenced. Furthermore, we 
      demonstrate that both CXCL12 and EGF induce Ca(2+) mobilization and IK(Ca) 
      channel activation but only CXCL12 induces a long-term upregulation of the IK(Ca) 
      channel activity. Furthermore, the Ca(2+)-chelating agent BAPTA-AM abolished the 
      CXCL12-induced, but not the EGF-induced, glioblastoma cell chemotaxis. In 
      addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 
      pathway is only partially implicated in the modulation of CXCL12-induced 
      glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway 
      is not involved. In contrast, EGF-induced glioblastoma migration requires both 
      ERK1/2 and PI3K activity. All together these findings suggest that the efficacy 
      of glioblastoma invasiveness might be related to an array of nonoverlapping 
      mechanisms activated by different chemotactic agents.
FAU - Sciaccaluga, Miriam
AU  - Sciaccaluga M
AD  - Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, 
      Italy.
FAU - Fioretti, Bernard
AU  - Fioretti B
FAU - Catacuzzeno, Luigi
AU  - Catacuzzeno L
FAU - Pagani, Francesca
AU  - Pagani F
FAU - Bertollini, Cristina
AU  - Bertollini C
FAU - Rosito, Maria
AU  - Rosito M
FAU - Catalano, Myriam
AU  - Catalano M
FAU - D'Alessandro, Giuseppina
AU  - D'Alessandro G
FAU - Santoro, Antonio
AU  - Santoro A
FAU - Cantore, Giampaolo
AU  - Cantore G
FAU - Ragozzino, Davide
AU  - Ragozzino D
FAU - Castigli, Emilia
AU  - Castigli E
FAU - Franciolini, Fabio
AU  - Franciolini F
FAU - Limatola, Cristina
AU  - Limatola C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100414
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chelating Agents)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Recombinant Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Brain Neoplasms/*metabolism/pathology
MH  - Calcium Signaling
MH  - Cell Line, Tumor
MH  - Chelating Agents/pharmacology
MH  - Chemokine CXCL12/*metabolism
MH  - *Chemotaxis
MH  - Epidermal Growth Factor/metabolism
MH  - Glioblastoma/*metabolism/pathology
MH  - Humans
MH  - Intermediate-Conductance Calcium-Activated Potassium Channels/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Membrane Potentials
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/metabolism
MH  - Neoplasm Invasiveness
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Potassium Channel Blockers/pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA Interference
MH  - Receptors, CXCR4/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2010/04/16 06:00
MHDA- 2010/07/14 06:00
CRDT- 2010/04/16 06:00
PHST- 2010/04/16 06:00 [entrez]
PHST- 2010/04/16 06:00 [pubmed]
PHST- 2010/07/14 06:00 [medline]
AID - ajpcell.00344.2009 [pii]
AID - 10.1152/ajpcell.00344.2009 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2010 Jul;299(1):C175-84. doi: 
      10.1152/ajpcell.00344.2009. Epub 2010 Apr 14.