Down-regulation of CD9 expression and its correlation to tumor progression in B lymphomas.
Histological transformation, a pivotal event in the natural history of cancers including lymphomas, is typically associated with more aggressive clinical behavior. L3055, a B lymphoma cell line of germinal center (GC) origin, is dependent on follicular dendritic cells (FDCs) for survival and proliferation, similar to GC-B cells. However, L3055 cells become less FDC-dependent after prolonged culture, which is analogous to transformation in vivo. Comparison of two L3055 subclones (i.e., the FDC-dependent indolent clone 12 and the FDC-independent aggressive clone 33) by DNA microarray revealed that CD9 was the most differentially expressed gene (P = 0.05). L3055-12 expresses high levels of CD9 while L3055-33 does not. Reduced levels or loss of CD9 expression is also observed in other CD9-positive B lymphoma cell lines. The resultant CD9-negative cells grow faster than CD9-positive cells due to their greater resistance to apoptosis. Furthermore, CD9-negative cells are less dependent on FDCs for their survival and growth compared with CD9-positive cells. CD9 down-regulation in B lymphomas appears to be controlled epigenetically, mainly through histone modifications. These findings imply that CD9 is inversely correlated with B lymphoma progression, and CD9 inactivation may play an important role in B lymphoma transformation.
Yoon
Sun-Ok
SO
Laboratory of Cellular Immunology, 1514 Jefferson Highway, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Zhang
Xin
X
Freedman
Arnold S
AS
Zahrieh
David
D
Lossos
Izidore S
IS
Li
Li
L
Choi
Yong Sung
YS
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D060245:Tetraspanin 29
D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29