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Molecular Role of Complement C3a in Cutaneous Squamous Cell Cancer

By: Joseph Fanelli
Posted: Monday, April 29, 2019

The complement anaphylatoxin C3a may promote cell proliferation, migration, and stemness in patients with cutaneous squamous cell carcinoma, according to findings presented in the Journal of Cellular Molecular Medicine. These molecular activities, observed by Songmei Geng, MD, PhD, of the The Second Affiliated Hospital of Xi'an Jiaotong University, China, and colleagues, were also correlated with the activation of the Wnt and β‐catenin pathway.

“Our study elucidated a novel correlation between complement anaphylatoxin C3a and [cutaneous squamous cell carcinoma] stemness that helps to provide insights into [cutaneous squamous cell carcinoma] tumorigenesis,” the authors concluded.

The authors analyzed C3 expression in cutaneous squamous cell carcinoma cell lines A431, Tca8113, SCC13, HSC‐5, and HSC‐1 as well as in immortalized HaCaT keratinocytes. Proliferation and migration of the cancer were determined after C3a exposure.

C3 expression was found to be more highly expressed in all cancer cell lines than in HaCAT cells.  C3a treatment significantly promoted cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro-MMP1, and pro-MMP2 expression, which were impeded by the C3aR antagonist.

Additionally, the expression of stemness factors Sox-2, Nanog, Oct-4, c-Myc, and CD-44 was stimulated by C3a and slowed by C3aR disruption. C3a activated the Wnt and β‐catenin pathway, whereas the disruption of C3aR expression dampened tumor growth and the expression of Wnt‐1, β‐catenin, and Sox‐2 in the xenograft model.

“The effect of C3a could be antagonized by blocking C3aR with its specific antagonist, which suggests that C3aR activation may be required for [cutaneous squamous cell carcinoma] cell transformation,” the authors added.

Disclosure: The study authors reported no conflicts of interest.

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