Complement components C1r and C1s promote oral squamous cell carcinoma cell proliferation

Abstract

Objectives

Oral squamous cell carcinoma (OSCC), the most frequent cancer of the oral cavity, mostly arises from the mucosal epithelium and rarely from the odontogenic epithelium. However, it is unclear whether they share the same mechanisms of OSCC development. Recently, we clarified comprehensive gene expression patterns in pathological specimens of two types of OSCC (odontogenic epithelial and mucosal epithelial origin). In addition, the enrichment analysis demonstrated that the "COMPLEMENT" gene set was elevated in these tumor lesions. However, the role of this system in OSCC tumorigenesis remains unclear. Here, we aimed to investigate the involvement of complement components in OSCC development.

Methods

siRNA and shRNA were used to examine OSCC cell proliferation in vitro and in vivo and assess activation of intracellular signaling using western blotting technics. An MEK1/2-specific inhibitor was used to verify its effects on the expression of C1r and/or C1s, components of the classical complement pathway. C1s expression in OSCC pathological specimens was investigated using immunohistochemical analysis.

Results

C1r and/or C1s expression regulated ERK and/or AKT activation and promoted OSCC cell growth. In addition, activated ERK regulated the expression of C1r and C1s via a negative-feedback loop. Immunohistochemically, C1s was expressed in the tumor lesions and frequently showed high expression levels of both phosphorylated ERK and Ki-67, but not in the non-tumor regions of OSCC specimens.

Conclusions

The complement system may be a common molecular mechanism for OSCC tumorigenesis, which arises from different origins: odontogenic and mucosal epithelium. Elevated C1r/C1s expression contributes to OSCC cell proliferation.