BME PhD Defense Seminar: Ut-Binh Giang
Development of microbubbles in polydimethylsiloxane as a screening tool for correlating the metastatic potential of cancer cells via their growth characteristics
Determining the metastatic potential of cells, or the ability of cells to disseminate to various organs in the body, has been the focus of much research as it pertains to the progression of the disease state in many malignant cancers. In particular, the high metastatic potential of melanoma cells is responsible for its high mortality rate amongst all skin cancers, causing up to 75% of death to those who are affected. In this thesis work, we have developed a method to form spherical compartments called microbubbles (MBs) in polydimethylsiloxane (PDMS) which we use as cell culture constructs whose unique size (250 Âµm diameter) and physical architecture provide qualitative measurements of the ability of cancer cells to grow and metastasize from the seeded site. Specifically, three A375 melanoma cell lines (A375.P, A375.MA1, and A375.MA2) that have been produced through an in vivo selection process to have increasing metastatic potential (courtesy of Dr. Lei Xu, URMC Biomedical Genetics), are used to verify their metastatic potential. We show that their growth characteristics including their morphology, the migratory behavior and the clonogenic potential when grown in MB cell culture can be used as metrics to differentiate their metastatic potential. These results indicate that highly metastatic cells (A375.MA2) show spheroid formation, have a higher rate of radial migration from the MB compartment, and exhibit higher clonogenic potential compared to the less metastatic cells (A375.P). The ability to verify the metastatic potential of cancer cells by growth characteristics is advantageous in that the innate behavior of the cells can be observed and it becomes a more physiological relevant model system for further studies such as drug testing and isolating cancer stem cells.