期刊
CANCER LETTERS
卷 364, 期 1, 页码 59-69出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.04.026
关键词
Mantle cell lymphoma; Exosomes; B-lymphocytes; Endocytosis
类别
资金
- NIH [5R01CA139444-10]
- Dotan Hematology Center at Tel Aviv University
- Lewis Family Trust
- Israel Science Foundation [181/10, 41/11]
- I-CORE Program of the Planning and Budgeting Committee
- FTA: Nanomedicines for Personalized Theranostics of the Israeli National Nanotechnology Initiative
- Leona M. and Harry B. Helmsley Nanotechnology Research Fund
- NATIONAL CANCER INSTITUTE [R01CA139444] Funding Source: NIH RePORTER
Mantle cell lymphoma (MCL) is an aggressive and incurable mature B cell neoplasm. The current treatments are based on chemotherapeutics and new class of drugs (e.g. Ibrutinib (R)), which in most cases ends with tumor resistance and relapse. Therefore, further development of novel therapeutic modalities is needed. Exosomes are natural extracellular vesicles, which play an important role in intercellular communication. The specificity of exosome uptake by different target cells remains unknown. In this study, we observed that MCL exosomes are taken up rapidly and preferentially by MCL cells. Only a minor fraction of exosomes was internalized into T-cell leukemia and bone marrow stroma cell lines, when these cells were co-cultured with MCL cells. Moreover, MCL patients' exosomes were taken up by both healthy and patients' B-lymphocytes with no apparent internalization to T lymphocytes and NK cells. Exosome internalization was not inhibited by specific siRNA against caveolin1 and clathrin but was found to be mediated by a cholesterol-dependent pathway. These findings demonstrate natural specificity of exosomes to B-lymphocytes and ultimately might be used for therapeutic intervention in B cells malignancies. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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