PESO: In vitro Models of Metastatic Collagen Microtracks

PESO：转移性胶原微轨的体外模型

• 批准号: 1740900
• 负责人: Cynthia Reinhart-King
• 金额: $ 15.73万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1740900&HistoricalAwards=false
• 关键词: PESO; vitro; Models; Metastatic; Collagen

The primary objective of this NSF-NCI Physical and Engineering Sciences in Oncology (PESO) joint research project is to elucidate the mechanism that is responsible for metastasis and the leader-follower cell dynamics that emerge during metastatic invasion. Of the 7.9 million cancer-related fatalities reported every year worldwide, over 90 percent are believed to be the result of metastatic disease, in which a subset of cells from the original tumor spread throughout the body. The physical mechanisms employed by metastatic cancer cells to invade remain poorly understood. During metastasis, cells from the primary tumor acquire characteristics that enable them to escape and migrate through a mechanically and chemically heterogeneous stromal environment to establish secondary tumors. As cells migrate, they remodel the matrix by both degrading it and by using mechanical force to physically move fibers from their path. Data suggest that degradation and remodeling of the extracellular matrix by "leader" cells enables the escape of additional cells from the primary tumor, termed "follower" cells. In this project, the PI and collaborators will use tailored materials, microfabricated structures and approaches from cell and molecular biology to re-create the leader-follower dynamics found in vivo and probe the underlying mechanisms guiding leader-follower migration. The two major educational goals in this project are to bring tissue engineering to the elementary and middle school classroom, and to incorporate undergraduate students from primarily 4-year, undergraduate schools in research. The work will integrate the major research themes in this project into an inquiry-based, hands-on module that builds off of the PI's previous work with the Ithaca Sciencenter, a local "please-touch" children's science museum.The intellectual merits of this project are the creation of a novel, microfabricated platform to study cell invasion and the identification of the molecular mechanisms guiding the metastatic migration of cells. The broader impacts of this prject are the design and implementation of a workshop for grade school children on cell migration that will involve graduate and undergraduate students in the design and implementation of the workshop.

该NSF-NCI肿瘤学（PESO）联合研究项目的主要目标是阐明负责转移和领导者的转移者细胞动力学的机制，这些机制在转移性入侵期间出现。 在全球每年报道的790万次与癌症相关的死亡人数中，据信超过90％是转移性疾病的结果，其中原始肿瘤的一部分细胞分布在整个人体中。 转移性癌细胞侵袭的物理机制仍然了解不足。 在转移过程中，原发性肿瘤的细胞获得了特征，使它们能够通过机械和化学异质的基质环境逃脱和迁移，以建立二次肿瘤。 当细胞迁移时，它们通过降解矩阵和使用机械力来重塑矩阵，从而将纤维从其路径中移动。 数据表明，“领导者”细胞对细胞外基质进行降解和重塑，可以使其他细胞从原发性肿瘤中逃脱，称为“自助剂”细胞。 在该项目中，PI和合作者将使用量身定制的材料，微生物结构以及来自细胞和分子生物学的方法来重新创建在体内发现的领导者追随者动力学，并探测指导领导者迁移的潜在机制。 该项目的两个主要教育目标是将组织工程带到小学和中学教室，并将主要是4年的本科生的本科生纳入研究。 这项工作将将该项目的主要研究主题整合到一个基于查询的动手模块中，该模块是基于PI先前的工作与Ithaca Sciencenter建立的，ITHACA Sciencenter是一个本地的“请求”儿童科学博物馆。该项目的智力优点是该项目的新小说平台来创建细胞入侵和鉴定的细胞迁移和识别。 该计划的更广泛的影响是针对小学生在细胞迁移的研讨会的设计和实施，这将涉及研究生和本科生的设计和实施研讨会。