Magnetically patterned co-cultures for cancer studies

用于癌症研究的磁性图案共培养物

基本信息

批准号：
7485706
负责人：
DANIEL H REICH
金额：
$ 14.62万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-17 至 2009-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Adhesive interactions between cancer cells and their surrounding microenvironment play a critical role in regulating the growth, development, and invasion of solid tumors. Direct adhesive contact between cancer cells and tissue stromal cells are thought to contribute to the survival, proliferation, and migration of cancers. However, the contribution of such heterotypic cell-cell interactions to the regulation of cancer cell function remains unclear because these interactions have been difficult to manipulate experimentally. This project will combine the expertise of two investigators to develop a novel system to juxtapose two cell types in micropatterned culture such that high fidelity heterotypic cell-cell interactions can be introduced in a controllable fashion in large numbers. The approach involves the use of magnetic nanowires, microfabricated arrays of magnetic traps, and engineering the adhesiveness of these traps to cells. The long-term goals of this project involve the development of a method to identify heterotypic cell-cell interactions that regulate the function of cancer cells. As a proof-of-concept, this novel approach will be used to identify cancer cell lines that increase proliferation in contact with one stromal cell, the endothelial cell. Specific Aim 1 will be to optimize and characterize the parameters that affect the yield and total number of cells trapped on the arrays that experience heterotypic cell-cell interactions. Specific Aim 2 will be to determine the effect of direct contact with endothelial cells on the proliferation of a model carcinoma cell line. Specific Aim 3 will be to demonstrate the use of this system with biochemical assays and to lay the groundwork for mechanistic studies of heterotypic cancer-stromal cell-cell pair interactions that modulate cancer proliferation. This research will apply recent advances in magnetic micro- and nanotechnology to develop a new approach to study the biology of cancer. The devices to be developed will enable studies of the interactions of cancer cells with surrounding healthy tissue that have not been possible previously. The increased understanding that this new approach will bring will have the potential to provide important input into efforts to control the growth and spread of cancer.

描述（由申请人提供）：癌细胞及其周围微环境之间的粘合性相互作用在调节实体瘤的生长，发育和侵袭中起关键作用。癌细胞和组织基质细胞之间的直接粘合性接触被认为有助于癌症的生存，增殖和迁移。但是，这种异型细胞 - 细胞相互作用对癌细胞功能调节的贡献尚不清楚，因为这些相互作用很难通过实验操纵。该项目将结合两名研究人员的专业知识，以开发一种新型系统，以在微图案培养中并置两种细胞类型，以便可以以大量可控的方式引入高富达异型细胞 - 细胞相互作用。该方法涉及使用磁性纳米线，磁陷阱的微生物阵列以及这些陷阱对细胞的粘附性。该项目的长期目标涉及开发一种方法来鉴定调节癌细胞功能的异型细胞相互作用。作为概念验证，这种新型方法将用于鉴定与一个基质细胞接触的癌细胞系，即内皮细胞。具体目标1将是优化和表征影响阵列中经历异型细胞 - 细胞相互作用的阵列中的单元格的参数和总数。具体目标2将是确定与内皮细胞直接接触对模型癌细胞系增殖的影响。具体目的3将是证明该系统与生化测定法的使用，并为调节癌症增殖的异型癌症 - 基细胞对相互作用的机械研究奠定基础。这项研究将应用磁性微技术和纳米技术的最新进展来开发一种研究癌症生物学的新方法。要开发的设备将能够研究癌细胞与以前无法使用的周围健康组织的相互作用。人们对这种新方法将带来的越来越多的理解将有可能为控制癌症的生长和传播提供重要的意见。