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Complement factor I promotes progression of cutaneous squamous cell carcinoma
Pilvi Riihilä1, Liisa Nissinen1, Mehdi Farshchian1
1Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
The Journal of Investigative Dermatology
|September 4, 2014
Summary
Complement factor I (CFI) is overexpressed in cutaneous squamous cell carcinoma (cSCC). Reducing CFI inhibits cSCC cell growth, migration, and tumor development, identifying it as a potential therapeutic target for this skin cancer.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (cSCC) incidence is increasing globally.
- The role of complement system components in cSCC progression requires further investigation.
Purpose of the Study:
- To investigate the role of complement factor I (CFI) in the progression of cutaneous squamous cell carcinoma (cSCC).
- To evaluate CFI as a potential therapeutic target for cSCC.
Main Methods:
- Analysis of cSCC cell lines and normal keratinocytes using whole transcriptome profiling, qRT-PCR, and western blotting.
- Immunohistochemical analysis of CFI expression in various skin lesions, including cSCC.
- In vitro experiments involving CFI knockdown and assessment of cell proliferation, migration, and ERK1/2 activation.
- In vivo studies using human cSCC xenograft models to evaluate the effect of CFI knockdown on tumor growth.
Main Results:
- Marked overexpression of complement factor I (CFI) was observed in cSCC cell lines compared to normal keratinocytes.
- CFI expression was significantly higher in invasive cSCCs and certain associated conditions compared to premalignant lesions and normal skin.
- Knockdown of CFI inhibited cSCC cell proliferation, migration, and extracellular signal-regulated kinase (ERK) 1/2 activation.
- Inhibition of CFI expression potently suppressed human cSCC xenograft tumor growth in vivo.
Conclusions:
- Complement factor I (CFI) plays a significant role in the progression of cutaneous squamous cell carcinoma (cSCC).
- CFI is identified as a potential therapeutic target for non-melanoma skin cancer, specifically cSCC.
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