Transfection of antisense core 2 beta1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells.
B-cell precursor (BCP) leukemia cells infiltrate into peripheral organs and the disease often relapses. Inhibition of tissue infiltration may improve the treatment outcome of BCP-leukemia patients. Selectin ligand has been suggested to play an important role in the infiltration of leukemia cells. However, the regulation mechanisms and involvement in tissue infiltration of selectin ligand expression in BCP-leukemia cells are not fully understood. In this study, we report that BCP-leukemia cells express selectin ligand on O-sialoglycoproteins. Core 2 beta1,6-N-acetylglucosaminyltransferase-1 (C2GnT-1) is mainly expressed in BCP-leukemia cells. Transfection of the antisense C2GnT-1 cDNA resulted in a significant reduction of either selectin ligand expression or selectin-dependent cell adhesion in BCP-leukemia cell line KM3 cells. Migration ability into mouse peripheral organs was reduced significantly in the antisense transfectant. These findings suggest that C2GnT-1 regulates selectin ligand expression. Downregulation of the selectin ligand expression level inhibits tissue infiltration of BCP-leukemia cells. C2GnT-1 may be a candidate of therapeutic target for the inhibition of infiltration of leukemia cells.
Kikuchi
J
J
Cell Regulation Analysis Team, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
Ozaki
H
H
Nonomura
C
C
Shinohara
H
H
Iguchi
S
S
Nojiri
H
H
Hamada
H
H
Kiuchi
A
A
Nakamura
M
M
D002465:Cell Movement; D018076:DNA, Complementary; D015536:Down-Regulation; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000473:pathology*; D008024:Ligands; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense; D019087:Selectins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D008024:Ligands; D016376:Oligonucleotides, Antisense; D019087:Selectins; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase