Classical pathway of complement system in cutaneous squamous cell carcinoma

Kristina Viiklepp, MD 

Department of Dermatology and Western Cancer Center (FICAN West), University of Turku and Turku University Hospital 

Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer in the world and it causes approximately 20% of skin cancer-related deaths. In addition, it is the sixth most common cancer in men and the seventh in women in Finland and the incidence of cSCC is increasing because of ageing of population. The most important risk factor is UV radiation. At present, there are no molecular markers for predicting which cSCC lesions are aggressive or metastasize rapidly. Inflammatory cells and factors are a part of cancers microenvironment and the complement system is very important part of human´s innate immunity and it regulates inflammatory processes. Our aim is to find biomarkers to predict the progression of cSCC. We are also trying to find new therapeutical targets. 

We have continued to study further the molecular mechanisms of C1r in cSCC. mRNA-seq was prepared for cSCC cells in which C1r was knocked down. Results of the pathway analysis of the genes regulated following C1r knockdown reveal association with GO terms: Protein targeting to membrane, Growth factor binding, Cell-matrix adhesion, Integrin binding; KEGG pathway: Focal adhesion and Reactome: Signaling by EGFR. We have prepared cSCC cell lines where C1r is knocked out with CRISPR/Cas9. We have used these C1r knockout cells in functional assays in culture and in vivo to study the molecular mechanisms of C1r in cSCC progression in more details. This part has been published in Journal of Investigative Dermatology. 

We study further the molecular mechanisms of C1q in cSCC. With Nanostring profiling we detected that C1q was upregulated in cSCC compared to normal skin. In addition, we did immunohistochemical staining of C1q and noticed significantly stronger staining in cSCC compared to AK and cSCCIS. We use multiplex IHC to study which cells produce C1q. Analyses are ongoing. We also study the intensity of C1q staining in cSCC and compare it to metastatic potential and clinical parameters. 

I have also started to write my thesis.