PESO: In vitro Models of Metastatic Collagen Microtracks

这个NSF-NCI肿瘤学物理和工程科学（PESO）联合研究项目的主要目标是阐明负责转移的机制以及转移侵袭过程中出现的领导-跟随细胞动力学。 在全世界每年报告的790万例癌症相关死亡中，超过90%被认为是转移性疾病的结果，其中来自原始肿瘤的细胞亚群遍布全身。 转移性癌细胞侵袭的物理机制仍然知之甚少。 在转移过程中，来自原发性肿瘤的细胞获得使它们能够逃逸并迁移通过机械和化学异质性基质环境以建立继发性肿瘤的特征。 当细胞迁移时，它们通过降解基质和使用机械力物理地将纤维从它们的路径移动来重塑基质。数据表明，“领导”细胞对细胞外基质的降解和重塑使得更多的细胞能够从原发性肿瘤中逃逸，这些细胞被称为“跟随”细胞。 在这个项目中，PI和合作者将使用定制的材料，微加工结构和细胞和分子生物学方法来重建体内发现的领导者-追随者动态，并探索指导领导者-追随者迁移的潜在机制。 该项目的两个主要教育目标是将组织工程带入小学和中学课堂，并将主要来自4年制本科学校的本科生纳入研究。 这项工作将把这个项目的主要研究主题整合到一个基于调查的实践模块中，该模块建立在PI之前与当地“请触摸”儿童科学博物馆Ithaca Sciencenter的工作基础上。这个项目的智力价值是创造一个新颖的微制造平台来研究细胞入侵和识别引导细胞转移迁移的分子机制。 这个项目的更广泛的影响是为小学生设计和实施一个关于细胞迁移的研讨会，研究生和本科生将参与研讨会的设计和实施。

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.