Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain

Yukinari Kato, Mika Kato Kaneko, Atsushi Kuno, Noboru Uchiyama, Koh Amano, Yasunori Chiba, Yasushi Hasegawa, Jun Hirabayashi, Hisashi Narimatsu, Kazuhiko Mishima, Motoki Osawa

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1301-1307
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number4
DOIs
Publication statusPublished - 2006 Nov 3

Keywords

  • Astrocytic tumors
  • Glioblastoma
  • Lectin array
  • NZ-1
  • Podoplanin
  • Tumor cell-induced platelet aggregation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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