Up-regulation of stromal cell-derived factor-1alpha and its receptor CXCR4 expression accompanied with epithelial-mesenchymal transition in human oral squamous cell carcinoma.

Stromal cell-derived factor 1alpha (SDF-1alpha) and its receptor CXCR4 have been implicated in the tumorigenesis, proliferation, and lymph node metastasis of cancer. Here, we report that highly invasive squamous cell carcinoma (SCC) cells with a spindle cell morphology show a strong expression of both SDF-1alpha and CXCR4. CXCR4 expression and cell migratory activity were further up-regulated by treatment with SDF-1alpha or TGF-beta1 in these cells. When epithelial-mesenchymal transition (EMT) was induced by Snail over-expression in SCC cells with an epithelial phenotype, an increased expression of SDF-1alpha was observed. Furthermore, SDF-1alpha and TGF-beta1 up-regulated the expression of CXCR4 and cell migratory activity in these cells. These results indicate that SDF-1alpha and CXCR4 expressions are possible markers of highly-invasive SCC and regulated by EMT.