Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3.

The mechanisms leading to squamous cell carcinoma of the head and neck (SCCHN) metastasis are incompletely understood. Although evidence shows that the chemokine receptor 7 (CCR7) and its ligand CCL19 may regulate tumor dissemination, their role in SCCHN is not clearly defined. CCR7 has been shown to regulate integrins, which facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (ECM). To investigate the relationship between CCR7 and integrin αvβ3 in metastatic SCCHN, we used adhesion and migration assays, immunofluorescence staining and western blotting to determine whether integrin αvβ3 can be activated by CCL19 in the metastatic SCCHN cell line PCI-37B, which was pre-incubated with CCL19 or the integrin αvβ3 inhibitor, IS201. Our results demonstrate that CCR7 favors PCI-37B cell adhesion and migration, induces reorganization of the actin cytoskeleton and induces integrin αvβ3 phosphorylation. The integrin αvβ3 inhibitor, IS201, blocked all of these effects. CCR7 and integrin αvβ3 expression significantly and positively correlated with tumor size, clinical stage and nodal metastasis. Taken together, our data indicate that CCR7 regulates cell adhesion and migration via integrin αvβ3 in metastatic SCCHN. These results should provide the groundwork for new strategies aimed at preventing SCCHN metastasis.