PESO: In vitro Models of Metastatic Collagen Microtracks

NSF-NCI肿瘤物理与工程科学(PISO)联合研究项目的主要目标是阐明转移的机制以及在转移侵袭过程中出现的领导-跟随细胞动力学。在全球每年报告的790万与癌症相关的死亡中，超过90%被认为是由转移性疾病造成的，转移性疾病是指原始肿瘤的一部分细胞扩散到全身。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，来自原发肿瘤的细胞获得的特征使它们能够逃脱并在机械和化学上不同的间质环境中迁移，从而建立继发性肿瘤。当细胞迁移时，它们通过降解基质和使用机械力将纤维物理地从其路径上移动来重塑基质。数据表明，“先导”细胞对细胞外基质的降解和重塑使额外的细胞能够从原发肿瘤中逃脱，这种细胞被称为“跟随”细胞。在这个项目中，PI和合作者将使用量身定做的材料、微制造结构和细胞和分子生物学的方法来重建体内发现的领导者-跟随者动力学，并探索引导领导者-跟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学带入中小学课堂，并将主要是四年制本科学校的本科生纳入研究。这项工作将把这个项目中的主要研究主题整合到一个以探究为基础的动手模块中，该模块建立在PI与伊萨卡科学中心之前的工作基础上，伊萨卡科学中心是当地的一家“请触摸”的儿童科学博物馆。这个项目的智力优势是创建了一个研究细胞入侵的新颖的微型制造平台，并确定了指导细胞转移迁移的分子机制。这一项目的更广泛影响是为小学儿童设计和实施一个关于细胞迁移的讲习班，让研究生和本科生参与讲习班的设计和实施。

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.