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）：癌细胞与其周围微环境之间的粘附相互作用在调节实体瘤的生长、发展和侵袭中发挥着关键作用。癌细胞和组织基质细胞之间的直接粘附接触被认为有助于癌症的存活、增殖和迁移。然而，这种异型细胞间相互作用对癌细胞功能调节的贡献仍不清楚，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，开发一种新颖的系统，将两种细胞类型并置在微图案培养中，从而可以以可控的方式大量引入高保真度的异型细胞间相互作用。该方法涉及使用磁性纳米线、微制造的磁陷阱阵列，以及设计这些陷阱对细胞的粘附性。该项目的长期目标包括开发一种方法来识别调节癌细胞功能的异型细胞间相互作用。作为概念验证，这种新方法将用于识别与一种基质细胞（内皮细胞）接触时增加增殖的癌细胞系。具体目标 1 是优化和表征影响阵列上经历异型细胞-细胞相互作用的细胞产量和总数的参数。具体目标 2 是确定与内皮细胞直接接触对模型癌细胞系增殖的影响。具体目标 3 将展示该系统在生化测定中的用途，并为调节癌症增殖的异型癌症-基质细胞-细胞对相互作用的机制研究奠定基础。这项研究将应用磁性微米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。即将开发的设备将能够研究癌细胞与周围健康组织的相互作用，这在以前是不可能的。这种新方法带来的更多了解将有可能为控制癌症生长和扩散的努力提供重要投入。