A 3D In Vitro Triculture Hybrid Model Recapitulating Tumor Stromal Interaction of Triple‐Negative Breast Cancer as a High Throughput Anticancer Drug Screening Platform

Abstract

AbstractBreast cancer (BC) progression is substantially driven by cellular cross‐talk between tumor and stromal cells within the tumor microenvironment (TME). However, lack of precise recapitulation of the heterocellular complexity, interactions in oversimplified 2D models, and physiological differences in animal models lead to discrepancy in anticancer drug response. Three‐dimensional (3D) in vitro bioengineered models that physiologically resemble in vivo TME are apt to overcome the discrepancy in the preclinical drug testing outcome. Here, a compartmentalized 3D in vitro triculture triple‐negative breast cancer (TC‐TNBC) model is bioengineered using silk‐fibroin (SF) scaffold and GelMA hydrogel for recapitulating stromal and tumor extracellular niche, respectively. The model features the cellular heterogeneity of stromal niche by incorporating most representative cell types in breast tissue, i.e., adipocytes and endothelial cells, and MDA‐MB‐231 cells in the tumor niche. The TC‐TNBC model exhibits enhanced tumorigenic potential in the presence of stromal cells. Screening of model anticancer drugs (doxorubicin (Dox) and cisplatin (Cis)) exhibits an increase in IC50 concentration in TC‐TNBC as compared to monoculture, suggesting crucial role of stromal cells in drug response. Drug sensitivity and cytotoxicity behavior mimick the in vivo like drug response. This model provides a facile and adaptable platform to represent tumor‐stromal heterogeneity and high‐throughput anticancer drug screening.