Document Detail


V-ATPase as an effective therapeutic target for sarcomas.
MedLine Citation:
PMID:  24416789     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Malignant tumors show intense glycolysis and, as a consequence, high lactate production and proton efflux activity. We investigated proton dynamics in osteosarcoma, rhabdomyosarcoma, and chondrosarcoma, and evaluated the effects of esomeprazole as a therapeutic agent interfering with tumor acidic microenvironment. All sarcomas were able to survive in an acidic microenvironment (up to 5.9–6.0 pH) and abundant acidic lysosomes were found in all sarcoma subtypes. V-ATPase, a proton pump that acidifies intracellular compartments and transports protons across the plasma membrane, was detected in all cell types with a histotype-specific expression pattern. Esomeprazole administration interfered with proton compartmentalization in acidic organelles and induced a significant dose-dependent toxicity. Among the different histotypes, rhabdomyosarcoma, expressing the highest levels of V-ATPase and whose lysosomes are most acidic, was mostly susceptible to ESOM treatment.
Authors:
Francesca Perut; Sofia Avnet; Caterina Fotia; Serena Rubina Baglìo; Manuela Salerno; Shigekuni Hosogi; Katsuyuki Kusuzaki; Nicola Baldini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental cell research     Volume:  320     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-01-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-32     Citation Subset:  IM    
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