Adipocytes enhance tongue cancer progression potentially via IL-6 and extracellular vesicles.

Obesity is associated with the increased incidence of various cancers. However, the connection between high body mass index and oral cancer risk is partly controversial, and the mechanistic role of adipocytes is largely unknown. We aimed to study the prognostic value and function of adipose tissue in oral tongue squamous cell carcinoma (OTSCC). The amount of adipocytes in OTSCC samples correlated positively with tumour size. High tumoural inflammatory cell count predicted better overall survival. Patient-derived adipose tissue and adipocytes (differentiated from adipose tissue-derived mesenchymal stem cells) induced the proliferation of OTSCC cells in vitro. Moreover, adipocytes increased the migration of cancer cells from both primary and metastatic sites without the need for direct cell-cell contact. Various cytokines, including interleukin 6 (IL-6), were present at high levels in adipocyte-OTSCC co-cultures, and inhibition of IL-6 signalling markedly reduced cancer cell migration. Moreover, the adipocyte-derived extracellular vesicles (EVs) induced OTSCC cell invasion. We conclude that adipocytes increase the proliferation of cancer cells and enhance their motility without direct cell contact. The protumourigenic effect of adipocytes is likely mediated by secreted cytokines, such as IL-6, and transported via EVs.