Abstract B51: Modeling the intrinsic and extrinsic influences on breast cancer phenotypic heterogeneity using mouse models and three-dimensional bioprinting

Breast cancer cells exhibit intertumoral and intratumoral heterogeneity due to both tumor cell intrinsic and extrinsic influence. We have been modeling phenotypic heterogeneity in breast cancer using multiple model systems to interrogate the causes of this heterogeneity as well as its effects on therapeutic resistance. Toward this end, we generated a novel, genetically-engineered mouse model of triple negative breast cancer driven by loss of PTEN in combination with low-level deregulated c-Myc expression. Expression of deregulated Myc significantly accelerates tumorigenesis in this model. Histologic and global gene expression analyses reveal that this model generates predominately two phenotypic groups within triple negative breast cancer. One group is composed of fibrotic tumors that have increased ECM deposition as well as increased alpha-Smooth Muscle Actin (SMA) and Fibroblast Associated Protein (FAP) expression in the stroma. These tumors express a Claudin-low molecular signature and have high p-SMAD3 expression. The second group is composed of adenocarcinomas that have less stromal involvement and decreased ECM deposition. In preliminary studies, the more fibrotic tumors exhibit increased resistance to targeted therapeutics. To better understand if this resistance is due to intrinsic or extrinsic influence, we are generating primary cultures of both the tumor and stromal cells from these mice. Through additional in vitro and in vivo studies, we will interrogate the mech...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Heterogeneity (Intratumor and Intertumoral): Poster Presentations - Proffered Abstracts Source Type: research