Abstract
β-Catenin is a key regulator of leukemia stem cell maintenance and drug resistance. Herein, we investigated the protective effects of the stromal cell-mediated VE-cadherin-β-catenin signal on Ph+ leukemia cells during imatinib treatment. We found stromal cells could desensitize imatinib and up-regulate VE-cadherin expression on Ph+ leukemia cells (K562 and SUP-B15 cells), which further stabilized and activated β-catenin. Knockdown of VE-cadherin with shRNA diminished the β-catenin protein and partly resensitized Ph+ leukemia cells to imatinib despite the presence of stromal cells, suggesting VE-cadherin is a potential target in the treatment of Ph+ leukemia.
Keywords:
Imatinib; Ph+ leukemia; Stromal cells; VE-cadherin; β-Catenin.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis*
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Antineoplastic Agents / pharmacology*
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Benzamides / pharmacology*
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Cadherins / biosynthesis*
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Cell Line, Tumor
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Coculture Techniques
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Drug Resistance, Neoplasm / drug effects*
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Gene Expression Regulation, Leukemic / drug effects*
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Humans
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Imatinib Mesylate
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K562 Cells
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Leukemia / drug therapy*
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Leukemia / metabolism
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Leukemia / pathology
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Neoplasm Proteins / biosynthesis*
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Philadelphia Chromosome*
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Piperazines / pharmacology*
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Pyrimidines / pharmacology*
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Signal Transduction / drug effects*
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Stromal Cells / metabolism
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Stromal Cells / pathology
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Up-Regulation / drug effects
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beta Catenin / biosynthesis*
Substances
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Antigens, CD
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Antineoplastic Agents
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Benzamides
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Cadherins
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Neoplasm Proteins
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Piperazines
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Pyrimidines
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beta Catenin
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cadherin 5
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Imatinib Mesylate