TY - JOUR
T1 - V-ATPase as an effective therapeutic target for sarcomas
AU - Perut, Francesca
AU - Avnet, Sofia
AU - Fotia, Caterina
AU - Baglìo, Serena Rubina
AU - Salerno, Manuela
AU - Hosogi, Shigekuni
AU - Kusuzaki, Katsuyuki
AU - Baldini, Nicola
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Chondrosarcoma
KW - Lysosomes
KW - Osteosarcoma
KW - Rhabdomyosarcoma
KW - V-ATPase
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UR - http://www.scopus.com/inward/citedby.url?scp=84888176031&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2013.10.011
DO - 10.1016/j.yexcr.2013.10.011
M3 - Article
AN - SCOPUS:84888176031
VL - 320
SP - 21
EP - 32
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -