Matrix Metalloproteinase-2 and -9 Secreted by Leukemic Cells Increase the Permeability of Blood-Brain Barrier by Disrupting Tight Junction Proteins Mechanism of Central Nervous System Leukemia
2011

Leukemic Cells Disrupt the Blood-Brain Barrier

Sample size: 46 publication 10 minutes Evidence: high

Author Information

Author(s): Feng Saran, Cen Jiannong, Huang Yihong, Shen Hongjie, Yao Li, Wang Yuanyuan, Chen Zixing

Primary Institution: Leukemia Research Unit, Jiangsu Institute of Hematology, 1st Affiliated Hospital, Soochow University, Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou, China

Hypothesis

MMP-2 and -9 secreted by leukemic cells play critical roles in the blood-brain barrier opening in CNS leukemia by disrupting tight junction proteins.

Conclusion

MMP-2 and -9 secreted by leukemic cells disrupt tight junction proteins, leading to increased permeability of the blood-brain barrier in CNS leukemia.

Supporting Evidence

  • MMP-2 and -9 were shown to disrupt tight junction proteins ZO-1, claudin-5, and occludin.
  • GM6001, an MMP inhibitor, reduced the permeability of the blood-brain barrier.
  • Leukemic cells exhibited higher invasion rates correlated with MMP-2 and -9 expression.
  • Animal models demonstrated that MMP-2 and -9 contribute to CNS leukemia progression.

Takeaway

Leukemic cells can break through the protective barrier of the brain by releasing special proteins that damage the connections between brain cells.

Methodology

The study used in vitro and in vivo models to examine the effects of MMP-2 and -9 on tight junction proteins in the blood-brain barrier.

Potential Biases

Potential bias in the selection of cell lines and animal models used in the study.

Limitations

The study primarily focused on specific leukemic cell lines and may not represent all types of leukemia.

Participant Demographics

The study involved male BALB/c nu/nu mice and human leukemic cell lines.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0020599

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