CD147 and the EGFR Signaling Cascade in Head and Neck Cancer

Abstract

Objectives:

Establish the relationship between two membrane bound proteins, CD147 and epidermal growth factor receptor (EGFR), through cutaneous squamous cell carcinoma (cSCC) cell lines.

Methods:

A pre-clinical investigation using three cSCC cell lines (Colo-16, SRB-1, and SRB-12) that were treated in vitro with a range of chimeric anti-CD147 mAb (0, 50, 100, 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration, and protein expression was then assessed. PCR analysis and immunofluorescent staining were also obtained. In vivo, Colo-16 xenografts were treated with anti-CD147 mAb (200µg i.p. triweekly), and tumors were then harvested for histologic analysis.

Results:

In response to anti-CD147 treatments there was a significant decrease in cell proliferation (P <.05) and migration in vitro (P < .001). These findings were confirmed with a Colo-16 SiCD147 cell line. Western blot analysis showed a decrease in not only CD147 expression but also the EGFR signaling cascade, specifically EGFR, BAD, and AKT. EGFR mRNA expression was decreased on PCR analysis in response to anti-CD147. In vivo response to anti-CD147 showed decreased tumor growth and, on histologic analysis, decreased CD147 and EGFR expression.

Conclusions:

Blocking CD147 inhibits cell growth in vitro and in vivo and results in downregulation of EGFR expression and signaling cascades. CD147 could be exploited as a therapeutic target in cSCC by modulation of the EGFR signaling pathway.