title: Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells.
abstract: Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant cells for the bone marrow (BM) milieu. The survival and proliferation of malignant plasma cells have been shown to rely on interactions with nonmalignant stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM microenvironment. However, the BM microenvironment is composed of a diverse array of cell types. This study examined the role of macrophages, an abundant component of BM stroma, as a potential niche component that supports malignant plasma cells. We investigated the proliferation of MM tumour cell lines when cultured alone or together with MSCs, macrophages, or a combination of MSCs and macrophages, using the carboxyfluorescein succinimidyl ester assay. Consistently, we observed increased proliferation of MM cell lines in the presence of either MSCs or macrophages compared to cell line-only control. Furthermore, the combined co-culture of MSCs plus macrophages induced the greatest degree of proliferation of myeloma cells. In addition to increased proliferation, MSCs and macrophages decreased the rate of apoptosis of myeloma cells. Our in vitro studies provide evidence that highlights the role of macrophages as a key component of the BM microenvironment facilitating the growth of malignant plasma cells in MM.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, USA. jkim@medicine.wisc.edu
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Denu
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Dollar
authors.forename: Leah E
authors.initials: LE
authors.lastname: Escalante
authors.forename: Justin P
authors.initials: JP
authors.lastname: Kuether
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Callander
authors.forename: Fotis
authors.initials: F
authors.lastname: Asimakopoulos
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology
chemical_list: D001897:Boronic Acids; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011719:Pyrazines; D000069286:Bortezomib