Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of complement component C3 and complement factor B (CFB) in the growth of cSCC. Analysis of cSCC cell lines (n = 8) and normal human epidermal keratinocytes (n = 11) with real-time quantitative PCR and Western blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell-specific labeling for C3 and CFB in invasive cSCCs (n = 71) and recessive dystrophic epidermolysis bullosa-associated cSCCs (n = 11) than in cSCC in situ (n = 69), actinic keratoses (n = 63), and normal skin (n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to benign papillomas. Knockdown of C3 and CFB expression inhibited migration and proliferation of cSCC cells and resulted in potent inhibition of extracellular signal-regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhibited growth of human cSCC xenograft tumors in vivo. These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as biomarkers and potential therapeutic targets in this metastatic skin cancer.
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Pilvi
P
Riihilä
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Liisa
L
Nissinen
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Mehdi
M
Farshchian
Department of Pathology, Turku University Hospital, Turku, Finland.
Markku
M
Kallajoki
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Atte
A
Kivisaari
Haartman Institute, University of Helsinki, Helsinki, Finland.
Seppo
S
Meri
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku, Finland.
Reidar
R
Grénman
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
Sirkku
S
Peltonen
Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
Juha
J
Peltonen
Oulu Center for Cell-Matrix Research, Biocenter Oulu and the Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Taina
T
Pihlajaniemi
Oulu Center for Cell-Matrix Research, Biocenter Oulu and the Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Centre for Cancer Biomarkers CCBIO, Department of Biomedicine, University of Bergen, Bergen, Norway.
Ritva
R
Heljasvaara
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.
Veli-Matti
VM
Kähäri
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism / Q000502:physiology*; D011415:Complement Factor B / Q000378:metabolism / Q000502:physiology*; D005260:Female; D064593:Heterografts; D006801:Humans; D008805:Mice, Inbred A; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D012878:Skin Neoplasms / Q000209:etiology*; D015854:Up-Regulation
D003176:Complement C3; D011415:Complement Factor B