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Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain
被引:143
作者:
Kato, Yukinari
Kaneko, Mika Kato
Kuno, Atsushi
Uchiyama, Noboru
Amano, Koh
Chiba, Yasunori
Hasegawa, Yasushi
Hirabayashi, Jun
Narimatsu, Hisashi
Mishima, Kazuhiko
Osawa, Motoki
机构:
[1] Natl Inst Adv Ind Sci & Technol, Res Ctr Glycosci, Open Space Lab C2, Tsukuba, Ibaraki 3058568, Japan
[2] Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan
[3] Saitama Med Sch, Dept Neurosurg, Moroyama, Saitama 3500495, Japan
[4] Tokai Univ, Sch Med, Dept Forens Med, Isehara, Kanagawa 2591193, Japan
关键词:
NZ-1;
podoplanin;
astrocytic tumors;
glioblastoma;
tumor cell-induced platelet aggregation;
lectin array;
D O I:
10.1016/j.bbrc.2006.08.171
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The mucin-type sialoglycoprotein, podoplanin (aggrus), is a platelet-aggregating factor on cancer cells. We previously described up-regulated expression of podoplanin in malignant astrocytic tumors including glioblastoma. Its expression was associated with tumor malignancy. In the present study, we investigated podoplanin expression and platelet-aggregating activities of glioblastoma cell lines. First, we established a highly reactive anti-podoplanin antibody, NZ-1, which inhibits podoplanin-induced platelet aggregation completely. Of 15 glioblastoma cell lines, LN319 highly expressed podoplanin and induced platelet aggregation. Glycan profiling using a lectin microarray showed that podoplanin on LN319 possesses sialic acid, which is important in podoplanin-induced platelet aggregation. Interestingly, NZ-1 neutralized platelet aggregation by LN319. These results suggest that podoplanin is a main reason for platelet aggregation induced by LN319. We infer that NZ-1 is useful to determine whether platelet aggregation is podoplanin-specific or not. Furthermore, podoplanin might become a therapeutic target of glioblastoma for antibody-based therapy. (c) 2006 Elsevier Inc. All rights reserved.
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页码:1301 / 1307
页数:7
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