Calorie restriction has no effect on bone marrow tumour burden in a Vk*MYC transplant model of multiple myeloma

Abstract

Multiple myeloma (MM) is an incurable haematological malignancy, caused by the uncontrolled proliferation of plasma cells within the bone marrow (BM). Obesity is a known risk factor for MM, however, few studies have investigated the potential of dietary intervention to prevent MM progression. Calorie restriction (CR) is associated with many health benefits including reduced cancer incidence and progression. To investigate if CR could reduce MM progression, dietary regimes [30% CR, normal chow diet (NCD), or high fat diet (HFD)] were initiated in C57BL/6J mice. Diet-induced changes were assessed, followed by inoculation of mice with Vk*MYC MM cells (Vk14451-GFP) at 16 weeks of age. Tumour progression was monitored by serum paraprotein, and at endpoint, BM and splenic tumour burden was analysed by flow cytometry. 30% CR promoted weight loss, improved glucose tolerance, increased BM adiposity and elevated serum adiponectin compared to NCD-fed mice. Despite these metabolic changes, CR had no significant effect on serum paraprotein levels. Furthermore, endpoint analysis found that dietary changes were insufficient to affect BM tumour burden, however, HFD resulted in an average two-fold increase in splenic tumour burden. Overall, these findings suggest diet-induced BM changes may not be key drivers of MM progression in the Vk14451-GFP transplant model of myeloma.

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

“…Similarly, in mice overexpressing TGFα, chronic caloric restriction (15%) provided better protection from tumor development than intermittent caloric restriction (40% of energy for 1 week every 4 weeks) [19]. In contrast to these results, chronic 30% caloric restriction had no effect on bone marrow and splenic tumor burden in a mouse transplant model of multiple myeloma [20].…”

Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma

“…Quantification of gene expression was achieved using RT 2 SYBR® Green reagent (Qiagen), on a QuantStudio™ 3 real‐time PCR system (Applied Biosystems) as previously described. 29 Sequences for mouse primers are outlined in Table S1 . Changes in gene expression were calculated relative to Gapdh using the ΔCt method (2 −ΔCt ).…”

Metabolites and Immune Response in Tumor Microenvironments

“…LEPR expression slows cell proliferation and promotes ALL differentiation by upregulating XBP1, involved in the unfolded protein response (UPR) pathway, and PRDM1, the tumor suppressor gene involved in T and B cell differentiation [258]. Calorie restriction has been shown to prevent the risk of radiation-induced myeloid leukemia in mice if performed both before and after irradiation [259]; however, it has no effect on multiple myeloma progression, although it is able to remodel the microenvironment of the bone marrow [260]. Therefore, the antitumor effects of CR and FMD are cancer specific and dependent on the genotypic and phenotypic characteristics of the tumors.…”