Cell-specific uptake of mantle cell lymphoma-derived exosomes by malignant and non-malignant B-lymphocytes.
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(®)), 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.
Laboratory of NanoMedicine, Department of Cell Research & Immunology, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
Inbal
I
Hazan-Halevy
Laboratory of NanoMedicine, Department of Cell Research & Immunology, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
Daniel
D
Rosenblum
Laboratory of NanoMedicine, Department of Cell Research & Immunology, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
Shiri
S
Weinstein
Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
Osnat
O
Bairey
Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
Pia
P
Raanani
Laboratory of NanoMedicine, Department of Cell Research & Immunology, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: peer@tauex.tau.ac.il.
Dan
D
Peer
D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D004705:Endocytosis; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
D034741:RNA, Small Interfering
B-lymphocytes; Endocytosis; Exosomes; Mantle cell lymphoma