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Towards a representative in vitro 3D model of tumor microenvironment in head and neck cancer: crosstalk between neoplastic cells and macrophages


Current therapies for head and neck squamous cell carcinoma (HNSCC) are focused on the neoplastic cells and have limited success, which is evidenced by the poor 5-year survival rate, high rate of recurrence and also by the fact that even smaller tumors treated only surgically can recur. In the past decade there has been a surge in the interest on the tumor microenvironment (TME) based on the relevant roles of non-neoplastic cells and extracellular matrix for tumor invasion and metastasis. Macrophages are the most abundant immune cell type in the TME of HNSCC and their numbers and phenotype are associated with tumor aggressiveness and response to treatment. However, in vitro studies mostly rely on bidimensional culture systems, which fail to recapitulate essential aspects of the TME, namely its tridimensional nature and particular components of the extracellular matrix. The aim of this application is to foster a new international research collaboration to develop a tridimensional model of TME in which the interactions between macrophages and HNSCC cells can be studied in the context of integrin signaling. This initial collaborative proposal intends to generate supporting/feasibility data that will be used in a future joint research application to be submitted, including the exchange of graduate students. The planned experiments will also add important information to the current FAPESP-funded application (Dr Rossa) and may validate candidate therapeutic targets and yield novel therapeutic approaches/strategies to improve the outcome of HNSCC patients. (AU)

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