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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 - 1 Jan 2014

Cite this

Perut, F., Avnet, S., Fotia, C., Baglìo, S. R., Salerno, M., Hosogi, S., ... Baldini, N. (2014). V-ATPase as an effective therapeutic target for sarcomas. Experimental Cell Research, 320(1), 21-32. https://doi.org/10.1016/j.yexcr.2013.10.011