Document Detail


Invasion of human glioma cells is regulated by multiple chloride channels including ClC-3.
MedLine Citation:
PMID:  21115901     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Glioblastoma is a type of highly malignant primary brain tumour. By means of ion excretion and the associated obligatory water loss, glioma cells can change shapes and undergo extensive migration and invasion. This study investigated the effects of inhibition of ion excretion in glioma cells.
MATERIALS AND METHODS: The expression of chloride channels (ClCs) and metalloproteinase-2 (MMP-2) was studied in two human glioma cell lines (STTG1 and U251-MG). The effects of ClC inhibition with chlorotoxin (a ClC-3 inhibitor), 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB) (a non-specific ClC inhibitor), and ClC-3 siRNA knockdown were studied.
RESULTS: Both STTG1 and U251-MG cells expressed ClC family members ClC-2, -3, -4, -5, -6 and -7, as well as MMP-2. Glioma cell invasion was markedly but not completely inhibited by ClC-3 and MMP-2 siRNA knockdown, and by chlorotoxin treatment. Addition of chlorotoxin to siRNA-treated glioma cells only slightly increased the suppression of invasion. In contrast, invasion was completely blocked by the non-specific ClC blocker NPPB.
CONCLUSION: ClCs are crucial in glioma cell migration and invasion. Blockade of a single ClC, however, is not sufficient to achieve complete inhibition of glioma cell invasion, suggesting that any future therapy should be targeted at pharmacological blockade of multiple ClCs.
Authors:
Vincent Chi Hang Lui; Steven Sin Sai Lung; Jenny Kan Suen Pu; Kwan Ngai Hung; Gilberto Kat Kit Leung
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4515-24     Citation Subset:  IM    
Affiliation:
Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, PR China.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Brain Neoplasms / genetics,  pathology*
Cell Adhesion / drug effects
Cell Movement / drug effects*
Cell Proliferation / drug effects
Chloride Channels / physiology*
Fluorescent Antibody Technique
Gene Silencing / physiology
Glioma / genetics,  pathology*
Humans
Immunoenzyme Techniques
Matrix Metalloproteinase 2 / physiology*
Neoplasm Invasiveness
Neurotoxins / pharmacology
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Scorpion Venoms / pharmacology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Chloride Channels; 0/Chlorotoxin; 0/ClC-3 channel; 0/Neurotoxins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Scorpion Venoms; EC 3.4.24.24/Matrix Metalloproteinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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