Elsevier

Laboratory Investigation

Volume 93, Issue 8, August 2013, Pages 921-932
Laboratory Investigation

Article
Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

https://doi.org/10.1038/labinvest.2013.86Get rights and content
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Abstract

Podoplanin (PDPN), one of the representative mucin-like type-I transmembrane glycoproteins specific to lymphatic endothelial cells, is expressed in various cancers including squamous cell carcinoma (SCC). On the basis of our previous studies, we have developed the hypothesis that PDPN functions in association with the extracellular matrix (ECM) from the cell surface side. The aim of this study was to elucidate the molecular role of PDPN in terms of cell adhesion, proliferation, and migration in oral SCC cells. Forty-four surgical specimens of oral SCC were used for immunohistochemistry for PDPN, and the expression profiles were correlated with their clinicopathological properties. Using ZK-1, a human oral SCC cell system, and five other cell systems, we examined PDPN expression levels by immunofluorescence, western blotting, and real-time PCR. The effects of transient PDPN knockdown by siRNA in ZK-1 were determined for cellular functions in terms of cell proliferation, adhesion, migration, and invasion in association with CD44 and hyaluronan. Cases without PDPN-positive cells were histopathologically classified as less-differentiated SCC, and SCC cells without PDPN more frequently invaded lymphatics. Adhesive properties of ZK-1 were significantly inhibited by siRNA, and PDPN was shown to collaborate with CD44 in cell adhesion to tether SCC cells with hyaluronan-rich ECM of the narrow intercellular space as well as with the stromal ECM. There was no siRNA effect in migration. We have demonstrated the primary function of PDPN in cell adhesion to ECM, which is to secondarily promote oral SCC cell proliferation.

CD44
cell adhesion
extracellular matrix
hyaluronan
oral squamous cell carcinoma
podoplanin

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Supplementary Information accompanies the paper on the Laboratory Investigation website

Podoplanin (PDPN), a glycoprotein specific to lymphatic endothelial cells, is a biomarker for oral cancer. This study elucidates the molecular role of PDPN in oral squamous carcinoma cells. PDPN, in collaboration with CD44, tethers the cells to extracellular matrices to inhibit their scattering but does not directly affect their proliferation and migration.

Supplementary information The online version of this article (doi:10.1038/labinvest.2013.86) contains supplementary material, which is available to authorized users.