Document Detail


V-ATPase as an effective therapeutic target for sarcomas.
MedLine Citation:
PMID:  24512745     Owner:  NLM     Status:  Publisher    
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 5.9-6.0pH) 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 highests 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     Date:  2013-10-25
Journal Detail:
Title:  Experimental cell research     Volume:  -     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2014-2-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 Published by Elsevier Inc.
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