title: Complement factor I promotes progression of cutaneous squamous cell carcinoma.
abstract: 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 (RT3) than in less tumorigenic HaCaT cell lines (HaCaT, A5, and II-4). The expression of CFI by cSCC cells was upregulated by IFN-γ and IL-1β. 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.
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Riihilä
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Nissinen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Farshchian
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Atte
authors.initials: A
authors.lastname: Kivisaari
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Ala-Aho
authors.affiliation: Department of Pathology, Turku University Hospital, Turku, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Kallajoki
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku, Finland.
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.affiliation: Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Sirkku
authors.initials: S
authors.lastname: Peltonen
authors.affiliation: Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland. Electronic address: veli-matti.kahari@utu.fi.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017244:Complement Factor I / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D011905:Genes, ras; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D012878:Skin Neoplasms / Q000473:pathology*
chemical_list: D017244:Complement Factor I