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Fatty Acid Binding Protein 5 is a Novel Target in Multiple Myeloma

ABSTRACT: To identify protein changes in human myeloma cancer cells resulting from FABP inhibition, we treated GFP+/Luc+MM.1S cells with the single inhibitors (50 µM BMS309405 or 50 µM SBFI-26) or the combination (50 µM of each) for 48 hour, isolated total cell proteins, and performed a mass spectrometry-based proteomic analysis.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma, Plasma Cell

DISEASE(S): Multiple Myeloma

SUBMITTER: Carlos Gartner

LAB HEAD: Calvin Vary

PROVIDER: PXD032829 | Pride | 2023-01-12

REPOSITORIES: Pride

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			Action	DRS
	gg_MFarrell_013122_IDA_BMS_01.wiff	Wiff
	gg_MFarrell_013122_IDA_BMS_01.wiff.scan	Wiff
	gg_MFarrell_013122_IDA_BMS_02.wiff	Wiff
	gg_MFarrell_013122_IDA_BMS_02.wiff.scan	Wiff
	gg_MFarrell_013122_IDA_COMBO_01.wiff	Wiff

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Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.

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Fatty Acid Binding Protein 5 is a Novel Target in Multiple Myeloma

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