Open AccessComplement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma
Author(s) -
Fan Zhuo,
Qin Jingjing,
Wang Dandan,
Geng Songmei
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13959
Subject(s) - cyclin d1 , cancer research , cell growth , biology , cell culture , gene knockdown , cell cycle , chemistry , cell , genetics
Background Complement C3 has been shown to be highly expressed in cutaneous squamous cell carcinoma ( cSCC ) tumour tissues and is correlated with tumour cell growth. This study aimed to investigate the mechanism of C3 in cSCC malignant transformation. Methods C3 expression was analysed in cSCC cell lines A431, Tca8113, SCC 13, HSC ‐5 and HSC ‐1 and in immortalized HaCaT keratinocytes. Proliferation and migration of cSCC were determined after C3a exposure. Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), pro‐matrix metalloproteinase 1 (pro‐MMP1), pro‐matrix metalloproteinase 2 (pro‐MMP2), stemness factors, GSK ‐3β, and β‐catenin were analyzed. Tumour growth was examined in a murine xenograft model. Results C3 expression was much more highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment significantly promoted cSCC cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro‐MMP1 and pro‐MMP2 expression, which were impeded by the C3aR antagonist. Moreover, the expression of stemness factors Sox‐2, Nanog, Oct‐4, c‐Myc and CD ‐44 was stimulated by C3a and slowed by C3aR disruption. Knockdown of Sox‐2 by si RNA transfection suppressed cell proliferation and migration, constrained VEGF secretion and inhibited pro‐ MMP 1 and pro‐ MMP 2 expression. C3a also activated the Wnt and β‐catenin pathway in cSCC cells. Disruption of C3aR expression dampened tumour growth and the expression of Wnt‐1, β‐catenin and Sox‐2 in the xenograft model. Conclusions C3a enhanced cell proliferation, migration and stemness in cSCC , and this activity was correlated with activation of the Wnt and β‐catenin pathway.