Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
Department of Pathology, Turku University Hospital, Turku, Finland.
Am J Pathol. 2017 May;187(5):1186-1197. doi: 10.1016/j.ajpath.2017.01.006. Epub 2017 Mar 17.
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.
皮肤鳞状细胞癌 (cSCC) 是最常见的转移性皮肤癌之一，发病率不断上升。我们研究了补体成分 C3 和补体因子 B (CFB) 在 cSCC 生长中的作用。实时定量 PCR 和 Western blot 分析 cSCC 细胞系 (n=8) 和正常人表皮角质形成细胞 (n=11) 显示 cSCC 细胞中 C3 和 CFB 表达上调。免疫组织化学染色显示，侵袭性 cSCC(n=71)和隐性营养不良性大疱性表皮松解症相关 cSCC(n=11)中肿瘤细胞特异性 C3 和 CFB 标记明显强于原位 cSCC(n=69)、光化性角化病(n=63)和正常皮肤 (n=5)。与良性乳头瘤相比，化学诱导的小鼠 cSCC 中 C3 和 CFB mRNA 表达显著上调。C3 和 CFB 表达的敲低抑制了 cSCC 细胞的迁移和增殖，并导致细胞外信号调节激酶 1/2 激活的强烈抑制。C3 和 CFB 的敲低显著抑制了人 cSCC 异种移植肿瘤在体内的生长。这些结果为 C3 和 CFB 在 cSCC 发展中的作用提供了证据，并将它们鉴定为这种转移性皮肤癌的生物标志物和潜在治疗靶点。
