VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers

Exp Hematol. 2010 Sep;38(9):733-43. doi: 10.1016/j.exphem.2010.05.001. Epub 2010 May 12.


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 of 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / pharmacology
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Brain / metabolism*
  • Brain / pathology
  • Cadherins / antagonists & inhibitors
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Humans
  • Lentivirus
  • Philadelphia Chromosome
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Transduction, Genetic / methods


  • Antibodies, Neutralizing
  • Antigens, CD
  • Cadherins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • cadherin 5