SDF-1/CXCR4 induces cell invasion through CD147 in squamous cell carcinoma of the hypopharynx.

Hypopharyngeal squamous cell carcinoma (SCC) has a poor prognosis due to local invasion and metastasis. The chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), play roles in tumor progression through unclear mechanisms. For the present study, we used a hypopharyngeal SCC cell line, FaDu, expressing CXCR4. We found that SDF-1 promotes migration and invasion of the FaDu cells. In addition, AMD3100, a specific antagonist of CXCR4, inhibited the binding of SDF-1 to CXCR4, resulting in a significant decrease in the FaDu cell migration induced by SDF-1. Stimulation of CXCR4 with SDF-1 induced an increase in the expression of CD147, a cell membrane protein; and this CD147 upregulation was abrogated by AMD3100. CD147 function-blocking antibodies also abolished the SDF-1-induced FaDu invasiveness. Our results suggested that SDF-1/CXCR4 mediate hypopharyngeal SCC cell migration and that CD147 is involved in the SDF-1/CXCR4-related tumor progression.