Effects on Radioresistance by the Tumor Microenvironment

One of the primary reasons in vitro therapeutic models lack high levels of efficacy is the inability to accurately model the natural tumor environment. These models only incorporate homogenous tumor cells and lack the complex nature of the tumor microenvironment. The extracellular matrix (ECM) found in tumors provides the structure and growth factors needed to undergo phenotypical changes such as Epithelial Mesenchymal Transition (EMT). EMT provides tumor cells with stem-cell-like characteristics and a resistance to treatment. Tumor spheroids coated in Matrigel® provide a three-dimensional testing modality that mimics radiation responses seen in clinical models. Interactions between tumor cell lines (SJSA osteosarcoma and SKBR3 breast cancer) and the laminin-rich ECM in three-dimensional culture provide a tumor niche that increases growth rate and more accurately represents treatment response. Radiation treatment given in fractionations showed changes in E cadherin expressions and NF-kB expression. This testing modality helps identify biomarkers associated with increased resistance to treatment. Creating a testing environment that allows in vitro therapeutic modeling to accurately represent in vivo tumor environments increases the efficacy of such studies