KSEF RDE: Physical Properties of Cancer Cells and Their Role in Metastasis: A Study Using Microchannels

Great strides have been made over the past 15 years in early detection and preventive measures for various types of cancer, however, cancer continues to be the second leading cause of death. More than half a million people succumb to the disease every year. In most cases, the ultimate cause of death is not the primary tumor itself, but the spread of this cancer from the primary tumor to other tissues and organs in the body. Hence, a very important aspect of cancer research should be the understanding of this metastatic cascade with the ultimate goal of developing techniques to inhibit this process. While the clinical importance of cancer metastasis is well recognized, advances in understanding the mechanisms involved in metastasis formation have lagged behind other cancer research developments. To metastasize, cancer cells must detach from the primary tumor, intravasate through the vessel wall to enter the blood stream, disseminate through the blood stream, and extravasate back through the vessel wall to reestablish in the interstitial tissue. While physiological properties are important in this process, it has been suggested that physical mechanisms such as adhesion and deformation are also important. The overall objective of the proposed investigation is to develop an in vitro engineered system to study adhesion and lodging of cancer cells in an environment that simulates in vivo flow conditions. Laser ablation microfabrication techniques will be used to produce microchannels containing endothelial cells that simulate the microvasculature. These microchannels will be optimized for geometric shape, size and endothelial cell growth and will be used to study cancer cell adhesion to the endothelial cells and lodging/deformation properties under controlled flow conditions. This study combines the expertise of Dr. Kimberly Anderson in cancer cell adhesion and deformation with the expertise of Dr. Janet Lumpp in laser processing of materials and is the first study of its kind that employs an engineered system to investigate cancer cell interactions in an environment that mimics both the geometry and hydrodynamic conditions of the in vivo circulation