Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain.
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.
Kato
Yukinari
Y
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Open Space Laboratory C-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. yukinari-k@bea.hi-ho.ne.jp
Kaneko
Mika Kato
MK
Kuno
Atsushi
A
Uchiyama
Noboru
N
Amano
Koh
K
Chiba
Yasunori
Y
Hasegawa
Yasushi
Y
Hirabayashi
Jun
J
Narimatsu
Hisashi
H
Mishima
Kazuhiko
K
Osawa
Motoki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D017434:Protein Structure, Tertiary; D051381:Rats; D000098853:Podoplanin
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008562:Membrane Glycoproteins; C092025:Pdpn protein, rat; D000098853:Podoplanin