Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma
Copyright policy )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.
- University of Turku Finland
- University of Helsinki Finland
- University of Bergen Norway
- Oulu University Hospital Finland
- University of Oulu Finland
EXPRESSION, skin, FACTOR-H, Skin Neoplasms, Carcinogenesis, Mice, Inbred A, FACTOR-I, alternative pathway, Mice, Nude, PROGRESSION, ALTERNATIVE PATHWAY, Pathology and Forensic Medicine, ACTIVATION, LUNG-CANCER, Cell Movement, Cell Line, Tumor, expression, tumor microenvironment, Animals, Humans, Aged, Cell Proliferation, Aged, 80 and over, HUMAN KERATINOCYTES, Complement C3, Middle Aged, ta3122, ta3125, Up-Regulation, Biomedicine, human keratinocytes, Case-Control Studies, lung-cancer, Carcinoma, Squamous Cell, factor-I, Heterografts, activation, Female, progression, TUMOR MICROENVIRONMENT, SKIN, Neoplasm Transplantation, factor-H, Complement Factor B
EXPRESSION, skin, FACTOR-H, Skin Neoplasms, Carcinogenesis, Mice, Inbred A, FACTOR-I, alternative pathway, Mice, Nude, PROGRESSION, ALTERNATIVE PATHWAY, Pathology and Forensic Medicine, ACTIVATION, LUNG-CANCER, Cell Movement, Cell Line, Tumor, expression, tumor microenvironment, Animals, Humans, Aged, Cell Proliferation, Aged, 80 and over, HUMAN KERATINOCYTES, Complement C3, Middle Aged, ta3122, ta3125, Up-Regulation, Biomedicine, human keratinocytes, Case-Control Studies, lung-cancer, Carcinoma, Squamous Cell, factor-I, Heterografts, activation, Female, progression, TUMOR MICROENVIRONMENT, SKIN, Neoplasm Transplantation, factor-H, Complement Factor B
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).82 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!