Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma.
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing globally. We have studied the expression of complement system components in cSCC. Expression profiling of cSCC cell lines (n=8) and normal human epidermal keratinocytes (n=5) with Affymetrix and quantitative real-time PCR (qPCR) revealed upregulation of complement factor H (CFH) and factor H-like protein-1 (FHL-1) in cSCC cell lines. The expression of CFH and FHL-1 mRNAs was also significantly higher in cSCC tumors (n=6) than in normal skin (n=11). Analysis of CFH and FHL-1 expression in vivo in invasive cSCCs (n=65), in situ cSCCs (n=38), and premalignant lesions (actinic keratoses, n=37) by immunohistochemistry showed that they were specifically expressed by tumor cells in cSCCs and the staining intensity was stronger in cSCCs than in in situ cSCCs and actinic keratoses. The expression of CFH by cSCC cells was upregulated by IFN-γ and the basal CFH and FHL-1 expression was dependent on extracellular signal-regulated kinase (ERK)1/2 and p38 signaling. Knockdown of CFH and FHL-1 expression inhibited proliferation and migration of cSCC cells and inhibited basal ERK1/2 activation. These results provide evidence for a role of CFH and FHL-1 in cSCC progression and identify them as progression markers and potential therapeutic targets in SCCs of skin.
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Pilvi M
PM
Riihilä
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Liisa M
LM
Nissinen
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Risto
R
Ala-Aho
Department of Pathology, Turku University Hospital, Turku, Finland.
Markku
M
Kallajoki
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku, Finland.
Reidar
R
Grénman
Haartman Institute, University of Helsinki, Helsinki, Finland.
Seppo
S
Meri
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
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; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001913:Bowen's Disease / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000378:metabolism*; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D000078404:Epidermal Cells; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D055623:Keratosis, Actinic / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008875:Middle Aged; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
D014408:Biomarkers, Tumor; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D034741:RNA, Small Interfering; D017242:Complement Factor H