Characterization of anti-podoplanin monoclonal antibodies: Critical epitopes for neutralizing the interaction between podoplanin and CLEC-2

Satoshi Ogasawara, Mika Kato Kaneko, Janet E. Price, Yukinari Kato

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Podoplanin (Aggrus) is a mucin-type sialoglycoprotein that is known as a useful marker for lymphatic endothelium and tumor-initiating cells (TICs). Interaction between podoplanin and C-type lectin-like receptor-2 (CLEC-2) is reported to be critical for podoplanin-induced platelet aggregation and cancer metastasis. Recently, several anti-human podoplanin antibodies have been created; however, these anti-podoplanin antibodies have not been well characterized. Five anti-podoplanin antibodies (NZ-1, D2-40, AB3, 18H5, and a rabbit polyclonal antibody) were investigated using ELISA, Western blot, and flow cytometry with synthesized podoplanin peptides and deletion mutants of recombinant podoplanin. The epitope of NZ-1 is platelet aggregation-stimulating (PLAG) domain-2/3; the epitope of D2-40, AB3, and 18H5 is PLAG1/2. The epitopes of D2-40 and AB3 are quite similar, although 18H5 is different from D2-40 and AB3. Using flow cytometric analysis, NZ-1 partially inhibited the interaction between podoplanin and CLEC-2, although other antibodies did not. In conclusion, the two most frequently used anti-podoplanin antibodies, D2-40 and AB3, have similar properties, although several studies have reported differences. NZ-1 neutralizes the interaction between podoplanin and CLEC-2, which may lead to the development of therapeutic antibodies against podoplanin-dependent cancer metastasis.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalHybridoma
Volume27
Issue number4
DOIs
Publication statusPublished - 2008 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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