Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis

2016 ◽  
Vol 35 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Jing-cheng Zhu ◽  
Meng-ya Si ◽  
Ya-zhen Li ◽  
Huan-zhu Chen ◽  
Zhi-cheng Fan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Central Nervous System Metastasis ◽  
Barrier Integrity ◽  
Blood Brain Barrier Integrity ◽  
Junction Proteins

scholarly journals Interleukin-34 Restores Blood–Brain Barrier Integrity by Upregulating Tight Junction Proteins in Endothelial Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115981 ◽  
Author(s):  
Shijie Jin ◽  
Yoshifumi Sonobe ◽  
Jun Kawanokuchi ◽  
Hiroshi Horiuchi ◽  
Yi Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity ◽  
Junction Proteins

scholarly journals Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood–Brain Barrier Integrity and Central Nervous System Homeostasis

Circulation ◽  
2016 ◽  
Vol 133 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Khiem A. Tran ◽  
Xianming Zhang ◽  
Dan Predescu ◽  
Xiaojia Huang ◽  
Roberto F. Machado ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

MMP-2 and MMP-9 Secreted by Leukemic Cells Increase the Permeability of Blood-Brain Barrier by Disrupting Tight Junction Proteins In Central Nervous System Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2694-2694
Author(s):  
Sa-ran Feng ◽  
Zi-Xing Chen ◽  
Jian-nong Cen ◽  
Hong-jie Shen ◽  
Li Yao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Acute Leukemia ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Abstract 2694 Recurrence of acute leukemia (AL) in the central nervous system (CNS) confers a poor prognosis. However, little is known about the the underlying mechanisms of leukemic cell infiltration into the CNS. The blood brain barrier (BBB) makes CNS become a refugee to leukemic cells and serves as a resource of cells that seed extraneural sites. Tight junction in brain microvessel endothelial cells (HMECs) constituted by tight junction proteins is an important structure of BBB. Except the well known role of degrading extracellular matrix in metastasis of cancer cells, here we identify matrix metalloproteinase 2 (MMP-2) and MMP-9 secreted by leukemic cells are also associated with BBB opening by degrading tight junction proteins. We have successfully established an animal model of CNS leukemia by using a highly invasive human acute monocytic leukemia cell line SHI-1 in nude mice. Multiple organs including skull and brain were sectioned and determined histopathologically for leukemia cell infiltration. The fact that the down- regulation of ZO-1, Claun-5 and Occludin accompanied with up-regulation of MMP-2 and MMP-9 was correlated with BBB breakdown in mice with CNS leukemia was found when examined by laser scanning fluorescence confocal microscopy and gelatin in situ zymography. The treatment with MMP-inhibitor GM6001 could significantly reverse these changes in tight junction proteins. In an in vitro monolayer BBB model made by human encephalo-microvessel endothelial cells and matreil gel, MMP-2 and MMP-9 specifically down-regulated ZO-1, Claun-5 and Occludin. Knock-down or inhibition of MMP-2 and MMP-9 expression protected ZO-1, Claun-5 and occludin from degradation and alleviated the permeability of BBB. Our findings suggest that the degradation of tight junction proteins ZO-1, Claun-5 and Occludin by MMP-2 and MMP-9 secreted by leukemic cells constitutes an important mechanism in BBB breakdown in CNS leukemia. These studies provide a potent evidence for future pharmacological treatment to inhibit the CNS involvement in acute leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Gpr124 is essential for blood–brain barrier integrity in central nervous system disease

2017 ◽  
Vol 23 (4) ◽  
pp. 450-460 ◽  
Author(s):  
Junlei Chang ◽  
Michael R Mancuso ◽  
Carolina Maier ◽  
Xibin Liang ◽  
Kanako Yuki ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Central Nervous System Disease ◽  
Nervous System Disease ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
System Disease ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity
Sign in / Sign up

Export Citation Format

Share Document