Complement Factor I Promotes Progression of Cutaneous Squamous Cell Carcinoma.

[dystrophic epidermolysis bullosa]

The incidence of cutaneous squamous cell carcinoma (cSCC ) is rising worldwide . We have examined the role of complement components in the progression of cSCC . Analysis of cSCC cell lines (n =8 ) and normal human epidermal keratinocytes (n =11 ) with whole transcriptome profiling (SOLiD ), quantitative real-time reverse transcriptase-PCR , and western blotting revealed marked overexpression of complement factor I (CFI ) in cSCC cells . Immunohistochemical analysis for CFI in vivo showed stronger tumor cell-specific labeling intensity in invasive sporadic cSCCs (n =83 ) and recessive dystrophic epidermolysis bullosa -associated cSCCs (n =7 ) than in cSCC in situ (n =65 ), premalignant epidermal lesions (actinic keratoses , n =64 ), benign epidermal papillomas (seborrheic keratoses , n =39 ), and normal skin (n =9 ). The expression of CFI was higher in the aggressive Ha-ras-transformed cell line (RT 3 ) than in less tumorigenic HaCaT cell lines (HaCaT , A 5 , and II -4 ). The expression of CFI by cSCC cells was upregulated by IFN-Î³ and IL -1 Î² . Knockdown of CFI expression inhibited proliferation and migration of cSCC cells and resulted in inhibition of basal extracellular signal-regulated kinase (ERK ) 1 /2 activation . Knockdown of CFI expression potently inhibited growth of human cSCC xenograft tumors in vivo . These results provide evidence for the role of CFI in the progression of cSCC and identify it as a potential therapeutic target in this nonmelanoma skin cancer .Journal of Investigative Dermatology advance online publication , 2 October 2014 ; doi :10 .1038 /jid .2014 .376 .