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dc.contributor.advisorFischbach-Teschl, Claudia
dc.contributor.authorLee, MinJoon
dc.description.abstractBreast cancer is the second leading cause of cancer-related deaths among women in the United States, and most of these deaths are due to metastasis to a secondary site, which is primarily the skeleton. The connection between primary breast cancer and frequent bone metastasis is poorly understood. Here, I investigate the role of two features of the bone microenvironment that may help elucidate this connection, the presence of mineral and mechanical stimuli. Bone marrow-derived mesenchymal stem cells (BM-MSCs) cultured with tumor-secreted soluble factors from bone-specific metastatic breast cancer cells deposited more mineral relative to factors from primary and lung-specific breast cancer cells, which could potentially explain the source of microcalcifications in the primary breast tumor. Additionally, I developed an in vitro loading system utilizing a mineralized 3-D model of the bone microenvironment. In the absence of loading, BM-MSCs in hydroxyapatite-containing (HA) scaffolds demonstrated enhanced osteoblastic activity compared to those in non-mineral containing control scaffolds. Under compressive loading, BM-MSCs cultured with tumor secreted soluble factors exhibited early commitment to the osteoblastic lineage. Loading did not affect breast cancer cell viability in this system, but expression of Runx2, a regulator of secretion of osteolytic proteins, was decreased 35% with loading. Taken together, these results suggest that bone marrow-derived stem cells are the source of microcalcifications, and metastatic tumor cells may affect the ‘vicious cycle’ by modulating the activity of osteoblasts and osteoclasts.
dc.subjectBiological sciences honors program
dc.subjectbreast cancer
dc.titleA novel hydroxyapatite-containing 3-D model to study the effects of mechanical loading on breast cancer bone metastasis
dc.typedissertation or thesis Sciences of Arts of Biological Sciences

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