Squamous cell carcinoma of the head and neck (HNSCC) metastasizes predictably to
locoregional, cervical lymph nodes. Tumor cells can express various receptors that facilitate
metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors
(CCRs), normally expressed on lymphocytes, control immune and inflammatory cell migration,
providing a link between innate and adaptive immunity. CCR expression was evaluated
in HNSCC, and we showed a consistent pattern of CCR6 downregulation and upregulation
of CCR7 in metastatic cells and tissues. Functional assays indicate that these surface receptors
were functional on metastatic tumor cells. CCR6 downregulation is consistent with its
decreased expression in cells emigrating from peripheral mucosal sites, while CCR7, important
for homing of immune cells to secondary lymphoid organs, was significantly upregulated.
Thus, CCR6, CCR7 and their ligands, normally important in controlling immune cell
trafficking in response to inflammatory stimuli, may have an important role in determining
the metastasis of HNSCC cells in vivo. Our data indicate that inhibition of CCR signaling
may provide a targeted molecular therapy to prevent HNSCC metastasis.
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