Podoplanin expression is upregulated in poorly differentiated cutaneous squamous cell carcinoma: Possible relationshop with the epithelial-mesenchymal-

Background: Podoplanin (PDPN), a transmembranous glycoprotein, which plays a crucial role in tumor migration and invasion, is a prognostic markers of various malignant tumors. However, its relationship with the differentiation grades of cutaneous squamous cell carcinoma (SCC) and the epithelial-mesenchymal-transition (EMT) remains unclear. Methods: The expression and distribution pattern of PDPN was examined using tissue sections obtained from 20 SCC cases (10 cases each of well- to moderately differentiated and poorly differentiated SCC), which were also analyzed with regard to the mesenchymal biological markers, vimentin and N-cadherin. Morphological and immunohistological analyses were also performed in keratinocytes with stable expression of PDPN (HaCaT-PDPN) by western blotting, RT-PCR, and immunostaining. Results: In well-differentiated SCC PDPN-expression was mostly restricted to the outermost layer of tumor nests. In poorly differentiated SCC, PDPN expression was stronger, with more diffuse distribution, and more samples had increased levels of vimentin and N-cadherin relative to highly differentiated SCC samples. HaCaT-PDPN cells had a spindle-shaped fibroblast-like appearance and expressed vimentin and N-cadherin together with the EMT-associated transcriptional factor, Snail. Conclusion: PDPN expression was increased and also more diffusely distributed in poorly differentiated SCC, which may be related to its occasional EMT-like phenotype.