Abstract
Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1α. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipose Tissue / metabolism*
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Adipose Tissue / pathology
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Animals
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Antibiotics, Antineoplastic / pharmacology*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Cell Line, Tumor
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Cell Movement / drug effects*
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Chemokine CXCL12 / metabolism
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Daunorubicin / pharmacology*
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Drug Resistance, Neoplasm / drug effects*
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Humans
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Mice
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Neoplasm Transplantation
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Transplantation, Isogeneic
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Tumor Microenvironment / drug effects*
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Vincristine / pharmacology*
Substances
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Antibiotics, Antineoplastic
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Antineoplastic Agents, Phytogenic
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Vincristine
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Daunorubicin