Modeling Bi-Directional Stromal-Cancer Cells Interactions with Engineered 3D Tumor Models

点击翻译按钮获取中文摘要

Cancer is a complicated set of diseases. Treatments have focused on the cancerous cells themselves. These efforts have neglected the cells surrounding the cancerous ones that contribute to the growth and durability of the tumor. Researchers also often deal with individual cells or small clusters of them, rather than a full, 3-dimensional mass of cells. This research will attempt to correct those limitations. A fully 3-dimensional mass containing the two cell types most prevalent in breast cancer tumors will be characterized. The results will be used to create a tumor simulation. Both the model and the experiment will be used to evaluate potential breast cancer drugs. High school students and college undergraduates will be included in the research activity, developing a stronger workforce for the growing biomanufacturing industry.This project will characterize the interactions between cancer cells and stroma cells within tumor microtissues in vitro. The information generated will be used to develop a 3-dimensional model of the tumor that includes cancer cells and stromal cells. The model system will include triple negative breast cancer (TNBC) cells and cancer-associated fibroblasts (CAF). The technology is based on aqueous two-phase systems that allow cell aggregation into spheroids. The spheroids are then embedded into a protein matrix containing stromal cells. Using the resulting tumor micro-tissues, we will test the hypothesis that activated stromal and TNBC cells synergistically co-regulate their extracellular matrix remodeling and that signaling with activated stromal cells confers drug resistance to TNBC cells. We will also investigate the efficacy of combination drug treatments of stromal and cancer cells to block stroma-mediated proliferative and drug resistance properties of cancer cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.