Effects on Radioresistance by the Tumor Microenvironment
Abstract
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.
Citation
Patel, Pankaj M (2018). Effects on Radioresistance by the Tumor Microenvironment. Doctoral dissertation, Texas A & M University. Available electronically from https : / /hdl .handle .net /1969 .1 /173341.