Galectin-1 supports the survival of CD45RA(-) primary myeloma cells in vitro.
The survival and proliferation of human myeloma cells are considered to be heavily dependent on the microenvironment of bone marrow (BM). This study confirmed that galectin-1 (Gal-1) and SDF-1alpha were produced by bone marrow mononuclear cells of myeloma patients. The addition of Gal-1 and SDF-1alpha to a serum-free synthetic medium, maintained the viability of primary myeloma cells for 2 weeks similar to that before culture. While Gal-1 reduced the viable cell number in CD45RA(+) B cell lines, it maintained the viability of CD45(-) U266 and CD45RA(-)RO(+) ILKM3 myeloma cell lines in the synthetic medium. This was confirmed with the transfection of the PTPRC (CD45) RA, -RB, or -RO gene into CD45(-) U266 cells. The combination of Gal-1 and SDF-1alpha significantly induced phosphorylation of Akt and IkB, while the phosphorylation of ERK1/2 was significantly reduced in CD45RA(+) U266 and Raji cells but not CD45(-) or CD45RA(-) U266 cells. Furthermore, we confirmed that Gal-1 bound to CD45RA in CD45RA(+) Raji cells, and also physically interacted with beta1-integrin by immunoprecipitation followed by Western blotting and confocal microscopy. The results suggest that Gal-1 has two different actions depending on its binding partner, and supports the survival of CD45RA(-) myeloma cells.
Abroun
Saeid
S
Laboratory of Cellular Signal Analysis, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan.
Otsuyama
Ken-Ichiro
K
Shamsasenjan
Karim
K
Islam
Abul
A
Amin
Jakia
J
Iqbal
Mohd S
MS
Gondo
Toshikazu
T
Asaoku
Hideki
H
Kawano
Michio M
MM
D001854:Bone Marrow Cells / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D066298:In Vitro Techniques; D019012:Integrin beta1; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt
D054377:Chemokine CXCL12; D037483:Galectin 1; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D019012:Integrin beta1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017493:Leukocyte Common Antigens