Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.01453
Keywords
brain metastasis of breast cancer; CXCR4; TRAIL; exosome; MSCs; lentiviral vector
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Funding
- National Natural Science Foundation of China [81472818]
- Fundamental Research Funds for the Central Universities
- Xinglin Young Talent Program of Shanghai University of Traditional Chinese Medicine
- Zhejiang Provincial Natural Science Foundation
- Public Welfare Research Project of Zhejiang Province [LGF19H140002]
- Zhejiang SCI-TECH University [11612932618290]
- China Postdoctoral Science Foundation [2019M662032]
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Strategies for treating brain metastases of breast cancer have demonstrated limited efficacy due to the blood-brain barrier (BBB). Gene therapy could improve the efficacy of chemotherapeutic drugs. Exosomes derived from the mesenchymal stem cells (MSCs) are small membrane-based gene vectors that can pass through the BBB. CXCR4 is the most commonly found chemokine receptor in human cancer cells. Furthermore, the SDF-1/CXCR4 axis plays an important role in the homing of MSCs for tumor cell diffusion and metastasis. TRAIL can selectively induce apoptosis in transformed cells without significant toxic side effects in normal tissues. In this study, exosomes were isolated from MSC(CXCR4+TRAIL)transduced with CXCR4 and TRAIL using a lentiviral vector. Synergistic antitumor study showed that exosome(CXCR4+TRAIL)exerted significant activity as a cooperative agent with carboplatin in an MDA-MB-231Br SCID mouse model, potentially engendering a novel strategy for advancing the treatment of brain metastases of breast cancer. Based on this study, further investigation of the effect of the vector on BBB and inducing apoptosis of brain tumors is warranted. In addition, the safety of the vector in animals during the treatment needs to be evaluated.
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