BIOMIMETIC MATRICES TO MODEL LUNG TUMORIGENESIS AND STAGES OF TUMOR PROGRESSION

Cancer is amongst the leading causes of mortality in the world. A deeper understanding of its biological complexity is necessary for developing novel diagnostic and therapeutic approaches. The appreciation of the role of microenvironment in regulating tumorigenesis and further stages of tumor progression opened new directions in the field of biomaterials. In recent years, in vitro cancer models have been engineered with an aim to recapitulate the important elements governing malignancy. Extracellular matrices (ECM) in native tissues regulate numerous cellular signaling events such as proliferation, adhesion and migration via mediating interaction of cells with bioactive ligands. Cancer tissues have been characterized with aberrant ECM content and structure, rendering it an attractive component to recapitulate in a biomaterial-based model of tumorigenesis to elucidate its role in cellular mechanisms leading to malignant transformation. Here, we propose to develop a biomaterial-based human in vitro model that will be used to study the role of ECM characteristics on lung tumorigenesis, tumor-associated angiogenesis, metastasis to secondary sites, and immune silencing mechanisms. Via achieving compositional and cellular complexity in the tumor model as well as tunability of mechanical properties, we aim to mimic the human lung tumor microenvironment and investigate the key signaling mechanisms that drive the stages of malignancy.