A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin.

Abstract

Podoplanin (PDPN/Aggrus/T1α), a platelet aggregation-inducing mucin-like sialoglycoprotein, is highly expressed in many cancers and normal tissues. A neutralizing monoclonal antibody (mAb; NZ-1) can block the association between podoplanin and C-type lectin-like receptor-2 (CLEC-2) and inhibit podoplanin-induced cancer metastasis, but NZ-1 reacts with podoplanin-expressing normal cells such as lymphatic endothelial cells. In this study, we established a cancer-specific mAb (CasMab) against human podoplanin. Aberrantly glycosylated podoplanin including keratan sulfate or aberrant sialylation, which was expressed in LN229 glioblastoma cells, was used as an immunogen. The newly established LpMab-2 mAb recognized both an aberrant O-glycosylation and a Thr55-Leu64 peptide from human podoplanin. Because LpMab-2 reacted with podoplanin-expressing cancer cells but not with normal cells, as shown by flow cytometry and immunohistochemistry, it is an anti-podoplanin CasMab that is expected to be useful for molecular targeting therapy against podoplanin-expressing cancers.

• Authors: Yukinari Kato, Mika Kato Kaneko
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 5924 (Aug 01 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 25080943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Membrane Glycoproteins
• PDPN protein, human

Topics

• Animals
• Antibodies, Monoclonal, Murine-Derived (biosynthesis, chemistry)
• Antineoplastic Agents (chemistry, metabolism)
• CHO Cells
• Cell Line, Tumor
• Cricetinae
• Cricetulus
• Glycosylation
• HEK293 Cells
• Humans
• Membrane Glycoproteins (chemistry, immunology)
• Mice, Inbred BALB C
• Protein Binding
• Protein Processing, Post-Translational