[[The]] effect of cellular and acellular components of the tumor microenvironment on both tumor and stromal cell phenotypes in a breast cancer model system

Abstract

Cancer progression is no longer thought of as being an independent event that is regulated by only the uncontrolled growth and genetic abnormalities of tumor cells. It has become increasingly apparent that differential biochemical signals from the tissue that surrounds the tumor, the tumor microenvironment (TME), as well as changes in the biophysical properties of the TME play important regulatory roles in the malignant progression of cancers. These extracellular cues alter intracellular signaling and gene expression leading to reciprocal alterations in the effect of tumor cells upon the microenvironment itself, furthering a vicious cycle of dysregulation in the cancer and the TME. This destabilization of tissue homeostasis induces behavioral changes in the cancerous cells, which eventually, inevitably, lead to metastatic disease. The work presented in this thesis examines the effect of specific alterations in the biophysical properties of the TME of breast cancer, upon both tumor cells and tumor associated cells.