Abstract P5-02-03: Phenotypic analysis for TNBC using 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. 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 show the model’s capabilities of supporting PDX tumor viability through flow cytometry on multiple PDX models as well as effects of human breast tissue on TNBC cell lines viability and proliferation. After showing the BC-MPS’ stability ex vivo, the effects on the cancer stem cell (CSC) population and lipid accumulation were explored through flow cytometry. Tu-BcX-4IC was seeded alone and in BC-MPS. After 7 days of incubation, the tumor was removed and the CSC population and lipid accumulation was measured through flow cytometry, showing an increase in CSC population and lipid accumulation when the PDX tumor was cultured in BC-MPS compared to cultured in 2D. Architectural changes that occur with the PDX explants when placed in BC-MPS were also monitored. The TNBC PDX model, Tu-BcX-4IC, was excised and seeded alone or in the BC-MPS system. The human breast tissue (HBT) and a PDX tumor piece was initially fixed in formalin before placed into BC-MPS (Day 0). After 4, 7, and 14 days of incubation, the 4IC PDX tumor explants seeded alone and in BC-MPS were fixed in formalin, paraffin embedded, and sectioned for H&E staining to determine the effect of the surrounding HBT on the PDX tumor. In additions to demonstrating the model’s capabilities of supporting PDX tumor viability and examining tumor architectural changes, assays were performed to test experimental capabilities of BC-MPS. Different BC cell lines were placed into the system and treated with chemotherapeutics to determine if the microphysiological system is capable of pharmaceutical studies. Here, we focus on the TNBC cell lines which were seeded alone and in the BC-MPS, and their response to the chemotherapeutic drugs, Paclitaxel, Romidepsin, and Cobimetinib. The proliferation response was monitored by luciferase imaging, demonstrating that BC-MPS can be used for drug studies.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 showing human tumor viability in BC-MPS, developing the model for personalized medicine. Citation Format: Katherine Hebert, Khoa Nguyen, Thomas Cheng, Madlin Alzoubi, Bridgette Collins-Burow, Elizabeth Martin, Frank Lau, Matthew Burow. Phenotypic analysis for TNBC using a novel breast cancer microphysiological system [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-02-03.