Association between YKL-40 and adult primary astrocytoma.
BACKGROUND
The YKL-40 coding chitinase 3-like 1 gene is 1 of the most overexpressed genes in human glioblastomas. The objectives of this study were to explore YKL-40 protein expression status and World Health Organization (WHO) pathologic grades of primary human astrocytoma and to investigate the role of YKL-40 in the proliferation of both established and primary astrocytoma cells in vitro.


METHODS
WHO grade 1, 2, 3, and 4 primary astrocytomas (210 patients) were evaluated for YKL-40 protein expression status in immunohistochemical analyses. In addition, after transfection with a plasmid that contained YKL-40 small-interfering RNA (siRNA), cell proliferation and the cell cycle were measured with a cell-viability assay and flow cytometry. Expression levels of phosphorylated, total mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) were detected by Western blot analysis.


RESULTS
The percentage of positive cells and the staining intensity differed significantly between different pathologic tumor grades (P < .001). The YKL-40 immunoreactivity score increased markedly with increased pathologic grade (F = 18.89; P < .001). In the in vitro experiment, the cell cycle was arrested in G(1) phase. An inhibitor of the p38 MAPK, SB203580, could partially abrogate the cell proliferation inhibition effect by siRNA treatment. The expression levels of phosphorylated extracellular signal-regulated kinase 1/2 and phosphorylated AKT were notably decreased in siRNA-transfected U87 cells. In contrast, the expression levels of phosphorylated p38 and phosphorylated c-jun N-terminal kinase 1 and 2 increased significantly (P < .01).


CONCLUSIONS
YKL-40 expression status correlated well with the pathologic grade of primary astrocytomas. The current results also indicted that YKL-40 plays a pivotal role in glioma cell proliferation through activation of the MAPK and AKT pathways. YKL-40 may be an attractive target for glioma therapy.
Zhang
Wei
W
Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Kawanishi
Masahiko
M
Miyake
Keisuke
K
Kagawa
Masahiro
M
Kawai
Nobuyuki
N
Murao
Koji
K
Nishiyama
Akira
A
Fei
Zhou
Z
Zhang
Xiang
X
Tamiya
Takashi
T
D054392:Adipokines; D000328:Adult; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D005910:Glioma / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D034741:RNA, Small Interfering