The role of platelet‐derived lysophospholipids in the progression of head and neck cancer

Abstract

Objectives. Platelets are known to have an important role in cancer progression but their function remains to be fully elucidated. In this study, we tested the hypothesis that platelet derived lysophospholipids are important in the spread and survival of head and neck cancer cells. Lysophospholipids are known to promote many of the hallmarks of cancer, including adhesion, proliferation, invasion and angiogenesis. Methods. In our study we utilised ‘paired’ primary and metastatic cell lines isolated from a primary tongue cancer lesion and a metastatic lymph node, respectively, from the same patient. This facilitates the study of the nature of head and neck cancer metastasis by comparing the local and metastatic neoplastic population from the same cancer. To investigate the role of lysophospholipids in squamous cell carcinoma of the tongue we compared the receptor profile of these cell lines at the RNA and protein level using PCR and flow cytometry. In addition, we analysed the functional significance of these findings using cell migration and chemoresistance assays. Results. We demonstrated for the first time that lysophospholipid receptors known to be critical in white blood cell migration are present in metastasising but not localised cancer cells. In addition, we proved that lysophospholipids are important in HNSCC migration and delineated many of the molecular pathways involved. Finally, we demonstrated that the presence of lysophospholipids protects cancer cells from chemotherapy‐induced apoptosis. Conclusions. Platelet derived lysophospholipids appear to be important in HNSCC metastasis. They may also explain why HNSCC nearly always metastasise to lymph nodes.