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

Biochem Biophys Res Commun. 2006 Nov 3;349(4):1301-7. doi: 10.1016/j.bbrc.2006.08.171. Epub 2006 Sep 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / immunology*
  • Cell Line, Tumor
  • Female
  • Glioblastoma / immunology*
  • Glioblastoma / pathology
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / immunology*
  • Protein Structure, Tertiary
  • Rats

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Membrane Glycoproteins
  • Pdpn protein, rat