Aurora-B dysfunction of multinucleated giant cells in glioma detected by site-specific phosphorylated antibodies.
OBJECTIVE
The origin of multinucleated giant cells in glioma has not been made clear. In a previous paper the authors studied multinucleated giant tumor cells by using mitosis-specific phosphorylated antibodies to determine the phosphorylation of intermediate filaments and demonstrated that these cells stay in the early mitotic stage, undergoing neither fusion nor degeneration. In the current study the authors investigated the possible genetic causes of multinucleated giant tumor cells.


METHODS
Cultured mono- or multinucleated human glioma cells were immunostained with monoclonal antibodies (mAbs) 4A4, YT33, TM71, HTA28, YG72, and alphaAIM-1. The three former antibodies revealed a particular mitotic cell cycle through site-specific phosphorylation of vimentin; that is, the early phase, mid phase, and late phase, respectively. The three later antibodies demonstrated phosphorylation of H3 at Ser28, phosphorylation of vimentin at Ser72, and aurora-B, respectively, making it possible to identify aurora-B distribution and function during mitosis. In addition, paraffin-embedded tissue sections obtained in three patients with giant cell glioblastoma were also examined. Multinucleated giant tumor cells immunoreacted with the mAb 4A4 and alphaAIM-1 but not with YT33, TM71, HTA28, and YG72 in vitro and in vivo.


CONCLUSIONS
Findings in this study indicated that multinucleated giant tumor cells remain in the early mitotic phase because of aurora-B dysfunction, effecting aberrations in cytoplasmic cleavage without affecting nuclear division.
Fujita
Mitsugu
M
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Japan.
Mizuno
Masaaki
M
Nagasaka
Tetsuro
T
Wakabayashi
Toshihiko
T
Maeda
Kenkou
K
Ishii
Dai
D
Arima
Toru
T
Kawajiri
Aie
A
Inagaki
Masaki
M
Yoshida
Jun
J
D000911:Antibodies, Monoclonal / Q000378:metabolism; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000201:enzymology* / Q000473:pathology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006657:Histones; D014746:Vimentin; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases