Objectives: To determine whether normal and malignant oral keratinocytes express functional XCR1.
Methods: Immunocytochemistry, flow cytometry and RT-PCR were used to demonstrate expression of XCR1 protein and mRNA on normal oral keratinocytes (NOK) and oral cancer cell lines (OCCL). Proliferation, migration and invasion assays were used to determine the response to lymphotactin with and without an XCR1 blocking antibody. The effect of lymphotactin on intracellular ERK1/2 pathway activation was determined by ELISA.
Results: NOK and OCCL (H357 & SCC4) expressed XCR1 protein and mRNA and responded specifically to lymphotactin by a significant increase in proliferation (P<0.05), migration (P<0.001) and invasion (P<0.0001). All of these effects were significantly reduced by an XCR1 blocking antibody (P<0.05). In addition, exposure to lymphotactin significantly up-regulated intracellular ERK1/2 phosphorylation in H357 cells (P<0.05).
Conclusions: These results show for the first time that functional XCR1 is expressed on both normal and malignant epithelial cells and that its ligand lymphotactin mediates cell migration, proliferation and invasion. This suggests that chemokines produced by lymphocytes have the potential to regulate oral epithelial cell behaviour in vivo and may play a role in both normal epithelial cell homeostasis and pathogenesis of oral cancer.