Chemokine Mediated Regulation of Tumor-Lymphatic Crosstalk in Head and Neck Cancers

Abstract

A number of cancers disseminate first through the lymphatic system, and the presence of tumor cells in the sentinel or draining lymph node is a major prognostic indicator. Head and neck cancers (HNSCC) which preferentially migrate through lymphatics remain one of the most common cancers with an incidence of 600,000 new cases worldwide and a poor prognosis of 5 years survival. Yet mechanisms that contribute to HNSCC metastasis through lymphatics remain very poorly understood. Metastasis to lymph nodes is strongly correlated to morbidity, so further investigation into the mechanisms and factors that lead to tumor-lymphatic crosstalk and promote lymphatic metastasis is needed. The goal of my research is to characterize the cross talk between lymphatic endothelial cells (LECs) and tumor cells and analyze specific chemokines, cytokines, and inflammatory genes involved. In addition, we also want to evaluate the tole of EMT associated genes in this mechanism. Recently, miRNA have emerged as significant predictors of disease outcome and in silico analysis was carried out to determine their role in EMT associated pathways in this tumor lymphatic crosstalk. This research will be very valuable for the implementation of specific therapeutic strategies that are targeting tumors that metastasize through the lymph node and identify specific molecular pathways that could be targeted to arrest tumors at the site of entry.