Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis

We examined the role of macrophage inflammatory protein (MIP)-3 alpha on oral cavity squamous cell carcinoma (OSCC) and whether it was involved in modulating OSCC cell functions. The study population was comprised of 102 patients with OSCC. MIP-3 alpha levels in tissues were examined by immunohistochemistry and quantitative real-time RT-PCR. Effects of MIP-3 alpha on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference. We found that MIP-3 alpha was overexpressed in OSCC tumor cells. MIP-3 alpha expression was significantly higher in tumor cells vs. normal epithelial cells, as determined by both quantitative real-time RT-PCR and immunohistochemistry. Overexpression of MIP-3 alpha was significantly correlated with positive pN status (P = 0.036). Nevertheless, there were no correlations related to patient age, pT status, overall pathological stage, cell differentiation, or perineural invasion. The long-term disease-specific survival for patient subgroups stratified by the absence or presence of MIP-3 alpha overexpression was 70.9% vs. 54.7% (P = 0.041). Multivariate analysis indicated that MIP-3 alpha overexpression had a significantly lower disease-specific survival (hazard ratio: 2.158; P = 0.037). Additionally, in vitro suppression of MIP-3 alpha expression in OECM-1 cells using specific interfering RNAs attenuated cell migration and invasiveness. These findings suggest that MIP-3 alpha overexpression in OSCC is associated with a poorer prognosis for patient survival and contributes to tumor metastasis. (C) 2010 Elsevier Ltd. All rights reserved.