The potential role of podoplanin in tumour invasion

Abstract

Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body. Here, we revisit the mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways leading to single and collective cell invasion and discuss novel distinct concepts of tumour cell invasion.

Figure 1

Human tumour samples stained for E-cadherin (brown) and podoplanin (red) show single cell (A) and collective cell invasion (B). (A) This adenocarcinoma of the colon invades into the surrounding tissue by single cell invasion. Most of the cells of the tumour bulk (TU) express E-cadherin. Single cells invading the tissue (arrows) have downregulated E-cadherin. Podoplanin is not expressed in this cancer. (B) An oesophageal carcinoma has formed an invasive cone that migrates into the surrounding tissue. Podoplanin (red) is expressed in the outer edge of the invading tumour. The tumour cells continue to express E-cadherin (brown) and migrate collectively. Size bar=50 μm.

Figure 2

Two mechanisms are involved in the progression of an adenoma to a carcinoma: either the tumours undergo EMT, or they do not (non-EMT). In EMT, the expression profile of adhesion molecules, components of the cytoskeleton and transcriptional regulators is changed. Although non-EMT pathways of tumour invasion are less well studied, they also lead to alterations of the cytoskeleton and the adhesive apparatus. In addition, podoplanin and possibly other mucin-like transmembrane proteins are involved.