Calorie restriction has no effect on bone marrow tumour burden in a Vk*MYC transplant model of multiple myeloma
Alanah L Bradey1,2, Stephen Fitter1,2, Jvaughn Duggan1,2
1Myeloma Research Laboratory, Faculty of Health and Medical Sciences, School of Biomedicine, University of Adelaide, Adelaide, Australia.
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.
Insights
Calorie restriction (CR) did not impact multiple myeloma (MM) progression in mice, despite metabolic improvements. High-fat diets, however, increased splenic tumor burden, suggesting diet influences MM spread differently in various tissues.
Area of Science:
- Hematology
- Oncology
- Metabolic Research
Background:
- Multiple myeloma (MM) is an incurable blood cancer driven by plasma cell proliferation.
- Obesity is a risk factor for MM, but dietary interventions for prevention are understudied.
- Calorie restriction (CR) offers health benefits, including potential cancer prevention.
Purpose of the Study:
- To investigate the efficacy of CR in preventing multiple myeloma (MM) progression.
- To assess the impact of different dietary regimes (CR, normal chow, high-fat diet) on MM.
- To explore the relationship between diet-induced metabolic changes and MM tumor burden.
Main Methods:
- Mice were subjected to 30% CR, normal chow diet (NCD), or high-fat diet (HFD).
- Mice were inoculated with Vk*MYC MM cells to model cancer progression.
- Tumor progression was monitored via serum paraprotein, and bone marrow (BM) and splenic tumor burden analyzed by flow cytometry.
Main Results:
- CR induced weight loss, improved glucose tolerance, increased BM adiposity, and elevated adiponectin.
- CR did not significantly alter serum paraprotein levels or BM tumor burden.
- High-fat diet (HFD) led to a two-fold increase in splenic tumor burden compared to controls.
Conclusions:
- Diet-induced metabolic changes in the bone marrow (BM) may not be primary drivers of MM progression in this model.
- Dietary interventions like CR may not be sufficient to halt MM progression.
- High-fat diets might promote MM dissemination to extramedullary sites like the spleen.
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