Role of Complement C3 and C5 in Head and Neck Squamous Cell Carcinoma

Introduction:

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and associated with poor survival and outcome. For different cancer entities, the complement system was already described as an important part in the maintenance and progression of cancer cells. In this study, we are interested in the expression patterns of complement key proteins and their role in tumor cell survival and progression.

Methods:

Four different human HPV negative HNSCC cell lines (UT-SCC-16A/16B/60A/60B), primary cancer tissue and healthy mucosa from patients were examined for complement expression using molecular biological and biochemical methods. The impact of C3 was also investigated via siRNA-dependent removal. Additionally, the effect of C3a/C5a on the activation of key signaling proteins was analyzed.

Results:

The four cell lines show varying expression patterns for C3 and C5 and their corresponding anaphylatoxin receptors. In cancerous patient tissue these factors tend to be downregulated compared to their healthy controls. A possible effect of C3a/C5a on phosphorylation status was demonstrated for EGFR and Src whereas the downregulation of intracellular C3 has an impact on cellular survival.

Conclusions:

The complement system is an important player in regulating processes of maintenance and immune modulation in cancer. Understanding its role in HNSCC may head to promising and innovative therapy approaches. Since there are differences within the investigated HNSCC cell lines an individual examination might be necessary. Also, the discrimination between intra- and extracellular complement seems to be of importance for HNSCC.

Publication History

Publication Date:
23 April 2019 (online)