Inhibiting fatty acid binding proteins decreases multiple myeloma cell proliferation and increases efficacy of dexamethasone
Date of Award
USM Access Thesis
Master of Science (MS)
Michaela R. Reagan
Multiple myeloma (MM) is an incurable cancer of the plasma cell and currently only has a 5 year survival rate of 53%. MM cells depend on a multitude of cells within the bone marrow microenvironment to flourish and resist treatment-induced cell death. Bone marrow adipocytes (BMAd), which increase in number with aging and obesity, have been shown to support myeloma cells by inducing proliferation, migration, and drug resistance, and ultimately contributing to myeloma patient relapse from remission. Herein we confirm the pro-myeloma effects of BMAd conditioned media (CM) and investigate the effects of the family of proteins termed the fatty acid binding proteins (FABPs), which are expressed both by adipocytes and tumor cells themselves. We found that high levels of FABP5 in patient myeloma cells corresponds to poor overall and relapse free survival for MM patients. Moreover, we found that pharmacologically inhibiting fatty acid binding proteins negatively impact tumor burden in vitro and in vivo,ultimately leading to increased survival of tumor-bearing mice. In addition, when combined with FABP inhibitors, dexamethasone, a common anti-myeloma treatment, has increased efficacy in vitro. Overall, these data suggest that FABPs are a novel target in myeloma and that this is a potential new cancer therapeutic target should be developed fuither.
Farrell, Mariah, "Inhibiting fatty acid binding proteins decreases multiple myeloma cell proliferation and increases efficacy of dexamethasone" (2020). Student Scholarship. 8.
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