TY - JOUR
T1 - Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain
AU - Kato, Yukinari
AU - Kaneko, Mika Kato
AU - Kuno, Atsushi
AU - Uchiyama, Noboru
AU - Amano, Koh
AU - Chiba, Yasunori
AU - Hasegawa, Yasushi
AU - Hirabayashi, Jun
AU - Narimatsu, Hisashi
AU - Mishima, Kazuhiko
AU - Osawa, Motoki
PY - 2006/11/3
Y1 - 2006/11/3
N2 - 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.
AB - 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.
KW - Astrocytic tumors
KW - Glioblastoma
KW - Lectin array
KW - NZ-1
KW - Podoplanin
KW - Tumor cell-induced platelet aggregation
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UR - http://www.scopus.com/inward/citedby.url?scp=33748772794&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.08.171
DO - 10.1016/j.bbrc.2006.08.171
M3 - Article
C2 - 16979138
AN - SCOPUS:33748772794
VL - 349
SP - 1301
EP - 1307
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -