Merkel cell carcinoma (MCC) is a rare but highly aggressive skin tumor. It is characterized by frequent regional lymph node involvement, distant metastases and a high rate of recurrence. Pathogentically, a human polyomavirus (MCPyV) is linked to MCC. Tight junctions (TJs) form compartments in multicellular organisms by sealing the paracellular pathway of cell sheets. Down- as well as up-regulation of TJ proteins was described in several tumors. Before, we showed the induction of a variety of TJ proteins in MCC, but their functions remained elusive.

Methodology: 

Several MCC cell lines (MCCL) were established in our lab. We investigated whether the expression of TJ proteins is correlated to the formation of barrier-forming TJs as well as tumorbiological characteristics of MCC e.g. MCPyV status and proliferation. TJ structures were investigated by freeze fracture electron microscopy, TJ functionality by tracer assays and transepithelial resistance (TER) measurement.

Results: 

All MCCL strongly express ZO-1, ZO-2, and JAM-A, but they are heterogeneously positive for various claudins, tricellulin, and occludin. They do not establish a TER in 2D culture, but barrier-forming TJ were detected in 3D spheroids. The tracer stop can be reversibly abolished by EDTA. MCCL with different claudin composition show different complexity of TJ strands. There was no correlation of TJ protein expression to the presence of MCPyV, Large-T-expression and proliferation.

Conclusion: 

Merkel cell carcinoma cells are able to form functional tight junctions. Within a tumor, this may result in encapsulated areas with restricted access for immune cells and therapeutics.proliferation.