Master of Science
Anatomy and Cell Biology
Allan, Alison L.
The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts with soluble selectins. The mechanism underlying the pro-migratory effect of lung-derived selectins is independent of ezrin/radixin/moesin (ERM) or CREB phosphorylation. Future studies should be aimed at elucidating mechanisms by which lung-derived selectins exert their pro-migratory function and whether these proteins can be targeted therapeutically to reduce lung metastasis of breast cancer.
Khan, Sami U., "Lung-derived selectins interact with CD44 and enhance the migration of breast cancer cells" (2018). Electronic Thesis and Dissertation Repository. 5945.
Available for download on Monday, August 31, 2020