Evaluation of immunohistochemical staining with PMab-38, an anti-dog podoplanin monoclonal antibody, in various canine tumor tissues

Abstract

Podoplanin (PDPN) is a type I transmembrane sialoglycoprotein with O-glycosylation and a high content of sialic acid. PDPN has been reported to be expressed in various human tumors and promote tumor progression, epithelial-mesenchymal transition, and distant metastasis. PDPN is also expressed in cancer-associated fibroblasts (CAFs), which promote tumor growth. We have developed novel tumor specific anti-PDPN antibodies. PMab-38, which is an anti-dog PDPN monoclonal antibody, recognized PDPN expression in canine squamous cell carcinoma (SCC) and malignant melanoma. However, there has been no research into PMab-38 recognition of other types of tumors and systemic normal tissue. The objective of this study was to evaluate the staining positivity of PMab-38 by immunohistochemical staining of various paraffin-embedded canine tumor and systemic normal tissues. Immunohistochemical analysis revealed that PMab-38 positively stained tumor cells in 9/11 (82%) SCC and 9/11 (82%) pulmonary adenocarcinoma tissues. In the tumor stroma, large spindle-shaped mesenchymal cells, which were suspected to be CAFs, were stained by PMab-38 in almost all tumor types: 9/10 (90%) for anal sac adenocarcinoma and 11/12 (92%) for transitional cell carcinoma tissues. Almost all normal tissues were negatively stained with PMab-38 except part of the kidney glomerulus. Taken together, our findings provide evidence that various types of tumor cells were strongly stained by PMab-38, but most normal cells were not stained. These results indicate that PDPN recognized by PMab-38 might be a target for tumor antigen targeting therapy. Further studies are required to investigate the anti-tumor effect in various canine tumors by antibody therapy using PMab-38