V-ATPase as an effective therapeutic target for sarcomas

Francesca Perut, Sofia Avnet, Caterina Fotia, Serena Rubina Baglìo, Manuela Salerno, Shigekuni Hosogi, Katsuyuki Kusuzaki, Nicola Baldini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalExperimental Cell Research
Volume320
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Chondrosarcoma
  • Lysosomes
  • Osteosarcoma
  • Rhabdomyosarcoma
  • V-ATPase

ASJC Scopus subject areas

  • Cell Biology

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