Mentors: Naveen Natesh, Sajeesh Kumar, Ph.D., Pankaj Mogha, Ph.D., Shyni Varghese, Ph.D. (Department of Bi0medical Engineering)
Clonal heterogeneity is regularly observed in primary and secondary cancers, but the precise role of each of these cell populations in tumor evolution and clinical prognosis remains poorly understood. Particularly, the functional significance of tumor clones in cancer metastasis is a point of ongoing investigation. Current research suggests the presence of tumor clones with a heightened metastatic potential that are more capable of metastatic colonization. In mouse models of sarcoma, secondary lesions in the lung have been observed to arise from a single metastatic clone, despite cellular heterogeneity in primary tumors and their presence in circulation. This observation could be attributed to the differences in extravasation potential of different cell populations or changes in colonization. We address these questions using an array of in-vitro platforms. First, we examined the changes in extravasation potential using a vascular network model. Next, we examined the changes in adhesion and proliferation of different cell populations by using lung explants cultures and decellularized lung extracellular matrix (ECM)-based cultures. Furthermore, we are quantifying the strength of the cell attachment in the lung ECM using a shear flow device. Characterizing these cellular differences offers the potential to identify specific clonal populations as therapeutic targets at different stages of metastasis.
