pubmed.ncbi.nlm.nih.gov

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

  • ️Sat Jan 01 2022

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

Alanah L Bradey et al. Sci Rep. 2022.

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.

© 2022. The Author(s).

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1

Effects of dietary regimens on body weight, composition and glucose tolerance at pre-tumour endpoint. (a) Experimental timeline showing duration of diets and analysis endpoints, (b) Body weight, (c) Fat mass, (d) Lean mass, (e) Fat mass (% body weight), (f) Lean mass (% body weight), (g) Fasting blood glucose levels, (h) Glucose clearance over time, (i) Fasting insulin levels, (j) HOMA-IR scores. Error bars SEM, (b–f) data n = 22–23/group, (g–k) data n = 10/group, ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ordinary one-way ANOVA with Tukey’s multiple comparisons test.

Figure 2
Figure 2

CR promotes proximal BM adiposity and an increase in serum adiponectin levels. (a) Representative images of osmium tetroxide stained tibias, (b) Total BMAT, (c) Proximal BMAT, (d) Distal BMAT, (e) Fasting serum adiponectin levels, (f) Fasting serum leptin levels, (g) Fasting serum IGF-1 levels. Error bars SEM, (a–d) n = 5/group, (e–g) n = 10/group, ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Ordinary one-way ANOVA with Tukey’s multiple comparisons test.

Figure 3
Figure 3

Peripheral blood cell counts at pre-tumour endpoint. (a) White blood cell count, (b) Neutrophil count, (c) Lymphocyte count, (d) Monocyte count, (e) Eosinophil count, (f) Basophil count, (g) % Neutrophils, (h) % Lymphocytes, (i) % Monocytes, (j) % Eosinophils, (k) % Basophils. Error bars SEM, n = 8–9/group, ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Figure 4
Figure 4

CR and HFD-feeding have no effect BM tumour burden. (a) Body weight over time, (b) Serum paraprotein levels over time, (c) Serum paraprotein levels at tumour endpoint (9 weeks post tumour initiation), (d) %GFP+ in the BM, (e) BM human MYC expression, (f) Correlation between %GFP+ in BM and BM human MYC expression, (g) Correlation between body weight and %GFP+ in BM, (h) Correlation between serum paraprotein and %GFP+ in BM. Error bars SEM, (a–e) n = 11–12 mice/group, ordinary one-way ANOVA with Tukey’s multiple comparisons test, (f–h) Combined data (n = 34 mice) from n = 11–12 mice/group, dot colours corresponds to diet group, blue dots: CR, black dots: NCD, red dots: HFD, correlation analysis, ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Figure 5
Figure 5

HFD promotes MM tumour growth in the spleen. (a) Spleen length, (b) Correlation between spleen length and body weight, (c) %GFP+ in spleen, (d) Splenic human MYC expression, (e) Correlation between %GFP+ in spleen and splenic human MYC expression, (f) Correlation between spleen length and %GFP+ in spleen, (g) Correlation between %GFP+ in spleen and serum paraprotein. Error bars SEM, (a,c) n = 10–12 mice/group, (d) n = 4–6 mice/group, Ordinary one-way ANOVA with Tukey’s multiple comparisons test, (e) Combined data (n = 15 mice) from n = 4–6 mice/group, (f,g) Combined data (n = 33 mice) from n = 10–12 mice/group, dot colours corresponds to diet group, blue dots: CR, black dots: NCD, red dots: HFD, correlation analysis, ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Similar articles

Cited by

References

    1. Ludwig H, Novis Durie S, Meckl A, Hinke A, Durie B. Multiple myeloma incidence and mortality around the globe; interrelations between health access and quality, economic resources, and patient empowerment. Oncologist. 2020;25:e1406–e1413. doi: 10.1634/theoncologist.2020-0141. - DOI - PMC - PubMed
    1. Kyle RA, et al. Prevalence of monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2006;354:1362–1369. doi: 10.1056/NEJMoa054494. - DOI - PubMed
    1. Kyle RA, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2018;378:241–249. doi: 10.1056/NEJMoa1709974. - DOI - PMC - PubMed
    1. Kyle RA, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2002;346:564–569. doi: 10.1056/NEJMoa01133202. - DOI - PubMed
    1. Rajkumar SV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–548. doi: 10.1016/S1470-2045(14)70442-5. - DOI - PubMed

Publication types

MeSH terms

Substances