Abstract 3201: Complement component C3 and complement factor B regulate growth of cutaneous squamous cell carcinoma

Abstract

Abstract Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing globally. We have examined the role of complement component C3 and complement factor B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) by quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB by cSCC cell lines was detected by western blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo by immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of both C3 and CFB was significantly upregulated by IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 by specific siRNAs inhibited migration of cSCC cells. Knockdown of CFB inhibited proliferation of cSCC cells and this was associated with potent inhibition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhibited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific biomarkers and putative therapeutic targets for invasive cSCC. Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. Complement component C3 and complement factor B regulate growth of cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3201. doi:10.1158/1538-7445.AM2015-3201