An anti-apoptotic role for galectin-3 in diffuse large B-cell lymphomas.
Increased resistance to apoptosis promotes lymphomagenesis with aberrant expression of cell survival proteins such as BCL-2 and c-MYC occurring in distinct lymphoma subtypes. Galectin-3 is an anti-apoptotic protein that protects T cells, macrophages, and breast carcinoma cells from death triggered by a variety of agents. We have found high levels of galectin-3 protein expression in a subset of B-cell neoplasms including diffuse large B-cell lymphoma (DLBCL), primary effusion lymphoma (PEL), and multiple myeloma (MM), in both cell lines and patient samples. However, we failed to detect galectin-3 in Burkitt lymphoma (BL), follicular lymphoma (FL), marginal zone lymphoma (MZL), MALT lymphoma or B-small lymphocytic lymphoma (B-SLL) cell lines or patient samples. To determine whether galectin-3 expression protects B cells from apoptosis, galectin-3-negative BL cells were transfected with a galectin-3 expressing plasmid, which resulted in markedly increased resistance to anti-Fas-induced cell death. In contrast, galectin-3-positive PEL cells transfected with an amino-terminal truncated galectin-3 vector showed increased sensitivity to anti-Fas induced apoptosis. During normal B-cell development, galectin-3 expression was lowest in germinal center and plasma B cells, from which DLBCL, PEL, and MM derive, and highest in long-lived naïve and memory B cells. This pattern of expression suggests that aberrantly increased galectin-3 levels in specific B-cell populations may yield a protective advantage during transformation and/or progression of certain B-cell neoplasms.
Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1732, USA.
Katrina K
KK
Hoyer
Mabel
M
Pang
Dorina
D
Gui
I Peter
IP
Shintaku
Ichiro
I
Kuwabara
Fu-Tong
FT
Liu
Jonathan W
JW
Said
Linda G
LG
Baum
Michael A
MA
Teitell
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D015153:Blotting, Western; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000502:physiology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D037502:Galectin 3