Generation of cells with Hodgkin's and Reed-Sternberg phenotype through downregulation of CD99 (Mic2).
Despite the fact that Hodgkin's and Reed-Sternberg (H-RS) cells are morphological hallmarks of Hodgkin's disease (HD), the nature of H-RS cells still remains to be resolved. Here we report that downregulation of CD99 (Mic2) leads to the generation of cells with an H-RS phenotype. IM9 and BJAB B-cell lines that were transfected with an antisense CD99 expression construct showed the morphological and immunological characteristics of H-RS cells such as multinuclearity, expression of CD15, decreased expression of major histocompatibility complex (MHC) class I and CD45RB, and deregulated secretion of cytokines. The reduced expression of CD99 was also confirmed in H-RS cells of patient's lymph nodes and three HD-derived cell lines, L428, KM-H2, and HDLM-2. Moreover, features characteristic of H-RS cells were completely abolished by forced expression of CD99 and by a constitutively active form of Rac, which functions downstream of CD99. We suggest that CD99 molecules play a crucial role in regulating functions and morphology of cells through a Rac-Rho signaling pathway and that the loss of CD99 expression is a significant molecular event to generate H-RS cells.
Kim
S H
SH
Departments of Pathology and Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Choi
E Y
EY
Shin
Y K
YK
Kim
T J
TJ
Chung
D H
DH
Chang
S I
SI
Kim
N K
NK
Park
S H
SH
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000473:pathology*; D014162:Transfection
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D016376:Oligonucleotides, Antisense; D017493:Leukocyte Common Antigens