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. ? ? ?
| Felton, Edward J; Copeland, Craig R; Chen, Christopher S et al. (2012) Heterotypic cell pair co-culturing on patterned microarrays. Lab Chip 12:3117-26 |
