Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Allan, Alison L.

Abstract

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.

Available for download on Monday, August 31, 2020

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