Ashley Kenworthy
Advisor: Dr. J. Matthew Kittelberger

Cancer stem cells (CSCs) have been determined to be populations of special cells within heterogeneous tumor cell populations that are able to maintain and even regenerate tumors. It has not been determined whether these CSCs originate from actual stem cells that have undergone a mutation and are promoting the cancer, or if the CSCs are differentiated cells that have reacquired stem cell-like properties. We examined the effects of Xanthosine (Xs) and 4-(Diethylamino)-benzaldehyde (DEAB) on two of The Wistar Institute's melanoma cell lines, WM3899 and WM1232. For various reasons, both of these drugs are hypothesized to promote the acquisition of stem-cell like phenotypes. Our aim was to determine if these drugs were indeed capable of causing these melanoma cells to acquire the properties of CSCs. Melcam, a common CSC marker protein, increased expression with each passage in the cells treated with Xs or DEAB, as detected by Flow Cytommetry Analysis, suggesting that the cells were acquiring stem cell properties. However, samples of cells from each of the treatments produced tumor growth in mice at a comparable rate to the control cells. Microarray analysis showed that many of the treated cells had improper regulation of particular genes and pathways related to DNA replication and repair, cell cycle regulation, and apoptosis, which are characteristics associated with CSCs. Interestingly, two different cell lines exhibited very different patterns of gene expression in response to drug treatment, suggesting that the cell lines were indeed responding differently to the treatments, as many types of melanoma do. Our data suggests that we were probably not successful in isolating a population of true CSCs, but we were able create a population of cells that had increased expression of stem-cell like properties.