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

癌症是一组复杂的疾病。治疗的重点是癌细胞本身。这些努力忽略了癌细胞周围的细胞，这些细胞有助于肿瘤的生长和持久性。研究人员还经常处理单个细胞或它们的小簇，而不是完整的三维细胞群。这项研究将试图纠正这些局限性。将表征包含乳腺癌肿瘤中最常见的两种细胞类型的全三维肿块。结果将用于创建肿瘤模拟。该模型和实验都将用于评估潜在的乳腺癌药物。高中生和大学生将参与研究活动，为不断发展的生物制造业培养更强大的劳动力。该项目将在体外表征肿瘤微组织中癌细胞和基质细胞之间的相互作用。生成的信息将用于开发包括癌细胞和基质细胞的肿瘤的三维模型。模型系统将包括三阴性乳腺癌（TNBC）细胞和癌症相关成纤维细胞（CAF）。 该技术基于含水两相系统，允许细胞聚集成球状体。然后将球状体包埋到含有基质细胞的蛋白质基质中。使用所得的肿瘤微组织，我们将测试活化的基质和TNBC细胞协同共调节其细胞外基质重塑以及活化的基质细胞的信号传导赋予TNBC细胞耐药性的假设。我们还将研究间质和癌细胞的联合药物治疗对阻断间质介导的癌细胞增殖和耐药性的功效。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.