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

Authors Si M, Jiao X, Li Y, Chen H, He P, Jiang F

Received 23 September 2017

Accepted for publication 28 November 2017

Published 12 February 2018 Volume 2018:10 Pages 305—313

DOI https://doi.org/10.2147/CMAR.S152419

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Mengya Si,1 Xiaoyang Jiao,2 Yazhen Li,2 Huanzhu Chen,2 Ping He,2 Fang Jiang1

1The First Affiliated Hospital of Shantou University Medical College, 2Cell Biology and Genetics Department, Shantou University Medical College, Shantou, People’s Republic of China

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 (P<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.

Keywords: CNS leukemia, cytokine, chemokine, U937, IL-60

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