Abstract PS8-20: Bc mps a novel breast cancer microphysiological system

Abstract

Abstract Breast cancer (BC) is among the most commonly diagnosed cancers in women and is the leading cause of malignant death in U.S. women. The triple negative breast cancer (TNBC) subtype is more aggressive and has a poorer prognosis compared to other subtypes. Few treatments exist for TNBC, partially due to limitations of current preclinical models. Current approaches to drug development in TNBC rely on simple, in vitro models. However, TNBCs are marked by cellular heterogeneity and complex interactions with the tumor microenvironment. Preclinical data from models that do not capture this complexity have yielded poor translational results. Patient derived xenografts (PDX), human tumors transplanted and grown in mice, are a newer, better model of TNBC. However, there are barriers when using mouse models: mice stroma can take over the PDX tumors, using immunocompromised mice can prevent immune responses and site-specific interaction, and mice are expensive. To overcome these barriers, a translational microphysiological system (MPS) was developed that is capable of maintaining the primary, human breast microenvironment in vitro. By seeding these MPS with breast cancer cell lines or tumor explants, we produce breast cancer MPS (BC-MPS).Here, we demonstrate BC-MPS’ stability ex vivo; the models remain healthy and viable for at least 2 weeks. This allows for long term studies on breast cancer and human breast tissue interactions. Different BC cell lines have been studied in the system. Initial comparisons between TNBC and ER+ cell lines showed a more aggressive remodeling of the human breast tissue (HBT) ECM by MDA-231 compared to MCF7. These cell lines have remained viable up to 14 days within the system. To examine the ability of BC-MPS to support PDX explant viability ex vivo, the TNBC PDX models 4QAN and 4IC were excised and seeded alone or in the BC-MPS system. After 6 days of incubation, viability was assessed by flow cytometry. Live/dead staining demonstrated that the 4QAN and the4IC PDX tumor explants have better viability in the BC-MPS model compared to being cultured in only media.After demonstrating the model’s capabilities of supporting PDX tumor viability, assays were performed to test experimental capabilities of BC-MPS. In addition to tumor architectural changes, cells in the system were treated with paclitaxel, and their response was monitored by luciferase imaging, demonstrating that BC-MPS can be used for drugstudies. BC-MPS is a promising new translational microphysiological system that facilitates studying long term interactions between real human breast tissue and cancer cells as well as the native tumor environment in HBT. The BC-MPS system’s ability to support the growth of established cell lines as well as PDXs has been demonstrated. Future studies will focus on developing the model for drug discovery studies. Citation Format: Katherine Hebert, Loren Brown, Khoa Nguyen, Madlin Alzoubi, Margarite Matossian, Bridgette Collins-Burow, Matthew Burow, Frank Lau. Bc mps a novel breast cancer microphysiological system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-20.