Abstract P3-01-16: Utilizing a decellularized patient-derived xenograft tumor model for the evaluation of triple negative breast cancer

Abstract

Abstract Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease with poorer prognoses compared to other breast cancer (BC) subtypes. This is due, in part, to the lack of clinically approved targeted therapeutics. The mechanisms underlying the process of recurrence in TNBC remain elusive. Traditional 2D BC models do not accurately mimic the cell-matrix interactions and extracellular matrix (ECM) composition that are vital to maintaining the tumor microenvironment and are unique to individual patient tumors. Here we introduce and utilize our novel decellularized patient-derived xenograft (PDX) TNBC model, TU-BcX-4IC (“4IC”), to address this knowledge discrepancy. In this study, we seeded TU-BcX-4IC PDX-derived cells onto TU-BcX-4IC PDX decellularized tumor scaffold (“4IC + 4IC scaffold”) and implanted our model into SCID/beige mice. Concordantly, mice were inoculated with TU-BcX-4IC cells mixed with Matrigel and PBS (“4IC + Matrigel”), or PBS alone (“4IC + PBS”). We demonstrate that our decellularized model, along with the injected cells, can form tumors in vivo. We also show that the “4IC + 4IC scaffold” model retains aberrant mitotic figures seen in the original 4IC PDX. However, due to inconsistent tumor growth in the experimental group, optimization of cell seeding onto our decellularized scaffold model is needed to produce consistent tumor propagation in vivo. We compared the number and area of metastases in the lungs and livers excised from the mice. The area and number of lung metastases were lower in mice implanted with “4IC + 4IC scaffold,” albeit not significantly. There was little difference in the area of liver metastases in all groups. The number of liver metastases was lower in the “4IC + Matrigel” and “4IC + 4IC scaffold” groups; however, there was no significance. All groups had a greater propensity to metastasize to the livers. We also compared differences in human and mouse ECM gene expression amongst all groups. Our decellularized scaffold model can be used as a platform to evaluate ECM onco-architecture and composition. The data presented here will help enhance our understanding of the breast tumor microenvironment and elucidate the mechanisms underlying tumorigenesis and recurrence in TNBC. Citation Format: Maryl Wright, Margarite Matossian, Connor King, Khoa Nguyen, Steven Elliott, Madlin Alzoubi, Elizabeth Martin, Bridgette Collins-Burow, Matthew Burow. Utilizing a decellularized patient-derived xenograft tumor model for the evaluation of triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-16.