Magnetically patterned co-cultures for cancer studies

用于癌症研究的磁性图案共培养物

• 批准号: 7289084
• 负责人: DANIEL H REICH
• 金额: $ 19.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/7289084
• 关键词: Accounting; Adhesiveness; Adhesives; Affect; Behavior; Biochemical; Biological; Biological Assay; Cancer Biology; Cancer cell line; Cause of Death; Cell Adhesion; Cell Communication; Cell Count; Cell Line; Cell physiology; Cells; Cellular biology; Coculture Techniques; Collaborations; Cultured Cells; Development; Devices; Diagnostic; Differentiation and Growth; Disease; Early Diagnosis; Economics; Endothelial Cells; Engineering; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Facility Construction Funding Category; Foundations; Gene Expression; Genomics; Goals; Growth; Growth and Development function; Healthcare Systems; Joints; Lead; Life; Link; Location; Magnetism; Malignant Epithelial Cell; Malignant Neoplasms; Measures; Methods; Microfabrication; Modeling; Monitor; Mutation; Nanotechnology; Numbers; Pattern; Pennsylvania; Play; Population; Publications; Rate; Regulation; Research; Research Design; Research Personnel; Role; Shapes; Signal Transduction; Solid Neoplasm; Stromal Cells; Students; Supervision; System; Techniques; Therapeutic; Thinking; Tissues; Transduction Gene; United States; Universities; Work; angiogenesis; base; cancer cell; cancer therapy; carcinogenesis; cell type; concept; cost; experience; improved; insight; magnetic beads; magnetic field; migration; mortality; nanoengineering; nanoscale; neovascularization; novel; novel strategies; particle; professor; response; retinal rods; tool; tumor; tumor progression

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（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、发展和侵袭中起着关键作用。癌细胞与组织基质细胞之间的直接黏附接触被认为有助于癌细胞的存活、增殖和迁移。然而，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在实验中操纵。该项目将结合两位研究人员的专业知识，开发一种新的系统，将两种细胞类型并置于微模式培养中，从而可以以可控的方式大量引入高保真异型细胞-细胞相互作用。该方法包括使用磁性纳米线，微制造的磁性陷阱阵列，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-细胞相互作用。作为一种概念验证，这种新方法将用于鉴定与一种基质细胞（内皮细胞）接触时增加增殖的癌细胞系。具体目标1将是优化和表征影响产量和被困在经历异型细胞-细胞相互作用的阵列上的细胞总数的参数。具体目的2将是确定直接接触内皮细胞对模型癌细胞系增殖的影响。具体目标3将展示该系统与生化分析的使用，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。这项研究将应用磁微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。即将开发的设备将使研究癌细胞与周围健康组织的相互作用成为可能，这在以前是不可能的。对这种新方法的进一步了解将有可能为控制癌症的生长和扩散提供重要的投入。