Increased circulating LDL cholesterol increases myeloma tumour burden in vivo

Gámez B., Morris EV., Olechnowicz S., Sowman, A., Turner, C. and Edwards CM. Multiple myeloma (MM) is a fatal malignancy characterized by an expansion of malignantplasma cells in the bone marrow (BM) and associated with osteolytic bone disease. MM ispreceded by the benign condition, monoclonal gammopathy of undetermined significance(MGUS). Understanding MGUS progression and development of MM bone disease is key forpatient management. We and others have previously demonstrated that diet-induced obesitypromotes myeloma progression, but the mechanisms underlying this remain unknown. The aimof the current study was to determine the effect of dietary cholesterol on MM development. A2% cholesterol diet was used to increase circulating LDL in mice. Mice were randomlydistributed to either a) cholesterol diet 4 weeks prior to 5TGM1 MM inoculation (pretreatment)or b) cholesterol diet 4 weeks prior to MM inoculation and continued for the entire experiment(continuous). Mice on the continuous cholesterol diet had increased tumour burden, associatedwith an increase in lipid droplet content of MM cells. No differences in tumour burden wereseen in those mice where cholesterol diet was halted at time of MM inoculation. In vitro,myeloma cells cultured with delipidated FBS had a 50% reduction in viability after 72 hours. Richcholesterol content lipoproteins (LDL) but not VLDL could restore MM cell viability, suggestingthat cholesterol is responsible for this lipid-depletion effect. Taken together, our results showthat high cholesterol promotes myeloma and results in a higher lipid content in myeloma cells,ultimately increasing BM tumour burden. Pretreatment with a cholesterol diet did not alterdisease progression suggesting a direct pro-tumourigenic effect of cholesterol. These resultsdemonstrate both the detrimental effect of cholesterol on myeloma progression and thepotential for dietary intervention approaches.