Investigation of proliferation and migration of tongue squamous cell carcinoma promoted by three chemokines, MIP-3[alpha] MIP-1 [beta], and IP-10

The aim of this work was to investigate the role of chemokines in proliferation and migration of tongue squamous cell carcinoma (TSCC). Out of the 80 cytokines surveyed by a human cytokine antibody array, three chemokines, macrophage inflammatory protein-3[alpha] (MIP-3[alpha]), macrophage inflammatory protein-1[beta] (MIP-1[beta]), and interferon gamma-induced protein 10 (IP-10), showed elevated expression in TSCC cells (CAL-27 and UM-1), compared to the oral mucosal epithelial cells. Immunohistochemistry confirmed the high level of expression of MIP-3[alpha] in the TSCC tissues, especially in the high clinical stages. Furthermore, Western blot and immunofluorescence staining indicated that C-C chemokine receptor type 5, C-C chemokine receptor type 6, and C-X-C motif chemokine receptor 3, which are the receptors for MIP-3[alpha], MIP-1[beta], and IP-10, respectively, were expressed in the TSCC cells. Viability assay showed MIP-3[alpha], MIP-1[beta], and IP-10 led to the proliferation of the CAL-27 cells. Interestingly, MIP-1[beta] and IP-10 also induced apoptosis in the TSCC cells. Transwell invasion assay showed MIP-3[alpha] and IP-10 could increase the invasive capability of TSCC cells; consistently, the enzymatic activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 increased in the MIP-3[alpha]- and IP-10-treated cells. In summary, our results indicate the expression of MIP-3[alpha], MIP-1[beta], and IP-10 increased in the TSCC cells. The elevated expression of MIP-3[alpha] and IP-10 promoted proliferation and migration of TSCC. These chemokines, along with their receptors, could be potential biomarkers and therapeutic targets for TSCC, especially for those in the high clinical stages. Keywords: MIP-3[alpha], MIP-1[beta], IP-10, tongue squamous cell carcinoma (TSCC)