PESO: Engineered Platforms to Investigate Molecular Determinants of Tumor Metastasis to Targeted Niche Sites

波士顿大学的PESO奖由材料研究部的生物材料项目授予，该项目由材料和表面工程项目（ENG/CMMI）共同创立；以及国家癌症研究所物理科学肿瘤学办公室（OPSO）。该奖项是为了表彰在生物学上相关的异型共培养系统的发展，作为肿瘤组织生长和进展的模型。该项目将实施综合实验和理论方法，以开发一个平台，以获得独特的物理测量集，可以深入了解肿瘤转移到体内特定部位的机制。这项工作的主要目的是：1)开发一种通过将细胞包裹在三维光聚合水凝胶中形成组织单位的新方法；2)评估肿瘤细胞与特定“转移生态位”细胞类型之间的相互作用；3)分离和回收每个细胞群进行生化和分子分析；4)发展一种理论方法来分析从工程系统获得的物理数据，以建立可以在系统中进行实验验证的理论模型。拟议的研究有望为肿瘤转移到特定生态位的机制提供见解。该奖项潜在的更广泛的科学影响可能是：1)阐明转移机制；2)发展替代物理测量来量化转移；3)潜在癌症治疗策略的发展。拟议项目的特点是一个综合研究和教育计划，旨在增加妇女和未被充分代表的少数民族研究人员进入劳动力市场的渠道。为了实现这些目标，该项目将通过波士顿大学的技术创新学者计划针对K-12学生，该计划将实施研究团队为波士顿地区学校开发的课程，这些学校有超过70%的少数族裔学生。这个项目的主要贡献将是建立一个生理相关的转移模型，该模型将工程、物理科学和应用数学方法结合起来。这项工作的潜在影响将是开发高通量筛选调节肿瘤-微环境相互作用的药物，最终，转移过程本身。该奖项的成果之一将是为肿瘤转移到体内特定部位的机制提供洞见。该奖项的最终目标是设计组装的组织单元，使其能够以受控的方式拆卸，从而能够分离和恢复每个细胞群，用于形态学，行为学，生化和分子分析。该奖项在科学上的广泛影响将是阐明转移的机制，发展转移的替代物理测量，以及发展新的癌症治疗方法。拟议的工作以综合研究和教育计划为特色，包括为波士顿大学的城市实验室开发课程，目标是当地的初中和高中学生和教师。该计划将开发模块，展示概念，应用程序和与生物材料一起工作的实践经验。模块的开发也将用于强调理论和实验模型系统的重要性。研究生和本科生将积极参与这些外展活动，这些学生将获得额外的教学和培训经验。该项目还将利用波士顿大学工程学院的“工程大使”项目，让本科生接触当地公立学校。

This PESO award to Boston University by the Biomaterials program in the Division of Materials Research is cofounded by the Materials and Surface Engineering program (ENG/CMMI); and the Office of Physical Sciences-Oncology (OPSO) of the National Cancer Institute. This award is for the development of a biologically relevant heterotypic co-culture system as a model for tumor tissue growth and progression. The project will implement an integrated experimental and theoretical approach for developing a platform to obtain unique sets of physical measurements that can provide insight into the mechanisms in which tumors metastasize to specific sites in the body. The major aims of this work are to: 1) develop a novel method of forming tissue units by encapsulating cells into 3-D photopolymerizable hydrogels; 2) evaluate the interactions between the tumor cells with a specific 'metastatic niche' cell type; 3) isolate and recover each cell population for biochemical and molecular analysis; and 4) develop a theoretical approach to analyze the physical data obtained from the engineered system to develop theoretical models that can be validated experimentally in the system. The proposed studies are expected to provide insight into the mechanisms by which tumors metastasize to specific niche sites. The potential scientific broader impacts of this award could be: 1) elucidation of the mechanisms of metastasis; 2) development of surrogate physical measurements to quantify metastasis; and 3) development of potential cancer treatment strategies. The proposed project features an integrated research and education program that seeks to increase the pipeline of women and underrepresented minority researchers into the workforce. To achieve these objectives, the project will target K-12 students through Boston University's Technology Innovation Scholars program, which will implement the curriculum developed by the research team for the Boston area schools that have more than 70% underrepresented minority students. The key contribution of this project would be the development of a physiologically relevant model of metastasis that integrates engineering, physical sciences and applied mathematical approaches. The potential impact of this work would be the development of high-throughput screening for agents modulating tumor-microenvironment interactions, and eventually, the metastatic process itself. One of the outcomes of this award would be in providing insight into the mechanisms by which tumors metastasize to specific sites in the body. The ultimate goal of this award will be to design the assembled tissue units such that they disassemble in a controlled manner, thereby enabling isolation and recovery of each cell population for morphological, behavioral, biochemical, and molecular analyses. The scientific broader impacts of this award would be in the elucidation of the mechanisms of metastasis, development of surrogate physical measurements of metastasis, and development of new cancer therapeutics. The proposed work features an integrated research and education program that includes the development of curriculum for Boston University's CityLab, which targets local area middle school and high school students and teachers. This program will develop modules that will demonstrate concepts, applications and hands-on experience in working with biomaterials. The development of modules will also be used to stress the importance of theoretical and experimental models systems. The graduate and undergraduate students will be actively involved in these outreach activities, and these students would gain additional experience in teaching and training. This program will also leverage Boston University's 'Engineering Ambassadors' program in the College of Engineering to engage undergraduate students in reaching out to local public schools.