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Stable tumor vessel normalization with pO_{2} increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment

Stable tumor vessel normalization with pO_{2} increase ...

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dc.contributor.author Kieda, Claudine pl
dc.contributor.author El Hafny-Rahbi, Bouchra pl
dc.contributor.author Collet, Guillaume pl
dc.contributor.author Lamerant-Fayel, Nathalie pl
dc.contributor.author Grillon, Catherine pl
dc.contributor.author Guichard, Alan pl
dc.contributor.author Dulak, Józef [SAP11012135] pl
dc.contributor.author Józkowicz, Alicja [SAP11114690] pl
dc.contributor.author Kotlinowski, Jerzy [SAP14001478] pl
dc.contributor.author Fylaktakidou, Konstantina C. pl
dc.contributor.author Vidal, Aurélien pl
dc.contributor.author Auzeloux, Philippe pl
dc.contributor.author Miot-Noirault, Elisabeth pl
dc.contributor.author Beloeil, Jean-Claude pl
dc.contributor.author Lehn, Jean-Marie pl
dc.contributor.author Nicolau, Claude pl
dc.date.accessioned 2015-07-06T09:48:24Z
dc.date.available 2015-07-06T09:48:24Z
dc.date.issued 2013 pl
dc.identifier.issn 0946-2716 pl
dc.identifier.uri http://ruj.uj.edu.pl/xmlui/handle/item/11638
dc.language eng pl
dc.rights Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa *
dc.rights.uri http://creativecommons.org/licenses/by/4.0/pl/legalcode *
dc.title Stable tumor vessel normalization with pO_{2} increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment pl
dc.type JournalArticle pl
dc.description.physical 883-899 pl
dc.description.additional Bibliogr. s. 897-899 pl
dc.abstract.en Tumor hypoxia is a characteristic of cancer cell growth and invasion, promoting angiogenesis, which facilitates metastasis. Oxygen delivery remains impaired because tumor vessels are anarchic and leaky, contributing to tumor cell dissemination. Counteracting hypoxia by normalizing tumor vessels in order to improve drug and radio therapy efficacy and avoid cancer stem-like cell selection is a highly challenging issue. We show here that inositol trispyrophosphate (ITPP) treatment stably increases oxygen tension and blood flow in melanoma and breast cancer syngeneic models. It suppresses hypoxia-inducible factors (HIFs) and proangiogenic/glycolysis genes and proteins cascade. It selectively activates the tumor suppressor phosphatase and tensin homolog (PTEN) in vitro and in vivo at the endothelial cell (EC) level thus inhibiting PI3K and reducing tumor AKT phosphorylation. These mechanisms normalize tumor vessels by EC reorganization, maturation, pericytes attraction, and lowering progenitor cells recruitment in the tumor. It strongly reduces vascular leakage, tumor growth, drug resistance, and metastasis. ITPP treatment avoids cancer stem-like cell selection, multidrug resistance (MDR) activation and efficiently enhances chemotherapeutic drugs activity. These data show that counteracting tumor hypoxia by stably restoring healthy vasculature is achieved by ITPP treatment, which opens new therapeutic options overcoming hypoxia-related limitations of antiangiogenesis-restricted therapies. By achieving long-term vessels normalization, ITPP should provide the adjuvant treatment required in order to overcome the subtle definition of therapeutic windows for in vivo treatments aimed by the current strategies against angiogenesis-dependent tumors. pl
dc.subject.en angiogenesis pl
dc.subject.en normalization pl
dc.subject.en oxygen pl
dc.subject.en PTEN pl
dc.subject.en tumor hypoxia pl
dc.description.volume 91 pl
dc.description.number 7 pl
dc.identifier.doi 10.1007/s00109-013-0992-6 pl
dc.identifier.eissn 1432-1440 pl
dc.title.journal Journal of Molecular Medicine pl
dc.language.container eng pl
dc.affiliation Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej pl
dc.subtype Article pl
dc.rights.original CC-BY; inne; ostateczna wersja wydawcy; w momencie opublikowania; 0; pl
dc.identifier.project ROD UJ / P pl
.pointsMNiSW [2013 A]: 40


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Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa Except where otherwise noted, this item's license is described as Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa