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细胞因子和趋化因子在白血病中枢神经系统转移中血脑屏障微环境中的作用。

The role of cytokines and chemokines in the microenvironment of the blood-brain barrier in leukemia central nervous system metastasis.

作者信息

Si Mengya, Jiao Xiaoyang, Li Yazhen, Chen Huanzhu, He Ping, Jiang Fang

机构信息

The First Affiliated Hospital of Shantou University Medical College.

Cell Biology and Genetics Department, Shantou University Medical College, Shantou, People's Republic of China.

出版信息

Cancer Manag Res. 2018 Feb 12;10:305-313. doi: 10.2147/CMAR.S152419. eCollection 2018.

DOI:10.2147/CMAR.S152419
PMID:29483784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5815469/
Abstract

AIM

Central nervous system (CNS) metastasis is a major obstacle in the treatment of leukemia, and the underlying mechanisms of leukemia CNS metastasis are not fully understood. The present study is an investigation of the role of the CNS microenvironment in leukemia CNS metastasis.

METHODS

Analog blood-brain barrier (BBB) was set by coculturing human brain microvascular endothelial cells (HBMVECs) and leukemia cells (U937 and IL-60), as well as HBMVECs and sera from leukemia patients, in vitro. The permeability of the HBMVEC monolayer and the levels of tight junction proteins, cytokines and chemokines (C&Ckines) were measured.

RESULTS

The permeability of HBMVECs increased when cocultured with leukemia sera. The expression of C&Ckines was significantly upregulated in HBMVECs cocultured with leukemia sera or leukemia cells, compared to the normal sera (<0.05, respectively). Specifically, significantly higher levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloprotease 9 (MMP-9) were found in HBMVECs and leukemia cells/sera coculturing systems.

CONCLUSION

Both leukemia cells and the molecules in leukemia sera play an important role in leukemia CNS metastasis. VEGF-A and MMPs may be the main factors resulting in the degradation of the BBB and inducing the CNS migration of leukemia cells.

摘要

目的

中枢神经系统（CNS）转移是白血病治疗中的主要障碍，白血病CNS转移的潜在机制尚未完全明确。本研究旨在探讨CNS微环境在白血病CNS转移中的作用。

方法

通过体外共培养人脑血管内皮细胞（HBMVECs）与白血病细胞（U937和IL - 60）以及HBMVECs与白血病患者血清来模拟血脑屏障（BBB）。检测HBMVEC单层的通透性以及紧密连接蛋白、细胞因子和趋化因子（C&Ckines）的水平。

结果

与白血病血清共培养时，HBMVECs的通透性增加。与正常血清相比，与白血病血清或白血病细胞共培养的HBMVECs中C&Ckines的表达显著上调（分别<0.05）。具体而言，在HBMVECs与白血病细胞/血清共培养体系中发现血管内皮生长因子A（VEGF - A）和基质金属蛋白酶9（MMP - 9）水平显著更高。

结论

白血病细胞和白血病血清中的分子在白血病CNS转移中均起重要作用。VEGF - A和基质金属蛋白酶可能是导致血脑屏障降解并诱导白血病细胞向中枢神经系统迁移的主要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/ef0bef051772/cmar-10-305Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/0fc3cfb14235/cmar-10-305Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/3368893f8da7/cmar-10-305Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/ef0bef051772/cmar-10-305Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/0fc3cfb14235/cmar-10-305Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/3368893f8da7/cmar-10-305Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e408/5815469/ef0bef051772/cmar-10-305Fig3.jpg

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2
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3
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