期刊
EXPERIMENTAL HEMATOLOGY
卷 38, 期 9, 页码 733-743出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2010.05.001
关键词
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资金
- WVU Microscope Imaging Facility (Morgantown, WV, USA) [P20 RR016440]
- National Institutes of Health (NIH, Bethesda, MD, USA) [R01 HL056888]
- NIH [P20 RR016440, R01 CA134573]
Objective. Infiltration of the central nervous system (CNS) by leukemia is a problematic disease manifestation of acute lymphoblastic leukemia (ALL). The mechanisms by which leukocytes interact with human brain-derived microvasculature endothelial cells (HBMEC) and enter the CNS are largely derived from models of inflammation. However, our data indicate that ALL cells do not elicit an inflammatory phenotype by HBMEC. Our current investigation focuses on the contribution of the unique coexpression of vascular endothelial (VE)-cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1) by ALL in mediating leukemic cell interactions with HBMEC as an in vitro model of the blood-brain barrier. Materials and Methods. Primary ALL and ALL cell lines were evaluated for VE-cadherin and PECAM-1 expression. Lentiviral-mediated transduction of VE-cadherin and PECAM-1 into REH cells and antibody neutralization of VE-cadherin and PECAM-1 in SUP-B15 cells was used to delineate the role or these two proteins in mediating ALL adhesion to, and migration through, HBMEC monolayers. Results. Although cell line models indicate that VE-cadherin and PECAM-1 expression is found on the surface Philadelphia chromosome-positive ALL, evaluation of primary ALL demonstrates that VE-cadherin and PECAM-1 are expressed independent of Philadelphia status. Expression of VE-cadherin and PECAM-1 by ALL enhanced the adhesion of ALL to HBMEC, while expression of PECAM-1 enhanced ALL adhesion to, and migration through, HBMEC. Conclusions. Expression of VE-cadherin and PECAM-1 by ALL cells positions them to interact with HBMEC. By increasing our understanding of molecular mechanisms through which ALL cells gain entry into the CNS, new strategies may be designed to prevent leukemia cell entry into the CNS. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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