High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6

Journal article


Publication Details

Author(s): Chen G, Luo Y, Eriksson D, Meng X, Qian C, Bäuerle T, Chen XX, Schett G, Bozec A
Journal: Oncotarget
Publication year: 2016
Volume: 7
Journal issue: 18
Pages range: 26653-69
ISSN: 1949-2553


Abstract


The impact of metabolic stress induced by obesity on the bone marrow melanoma niche is largely unknown. Here we employed diet induced obese mice model, where mice received high-fat (HFD) or normal diet (ND) for 6 weeks before challenge with B16F10 melanoma cells. Tumor size, bone loss and osteoclasts numbers were assessed histologically in the tibial bones. For defining the molecular pathway, osteopontin knock-out mice, interleukin 6 neutralizing antibody or Janus kinase 2 inhibition were carried out in the same model. Mechanistic studies such as adipocyte-melanoma co-cultures for defining adipocyte induced changes of tumor cell proliferation and expression profiles were also performed. As results, HFD enhanced melanoma burden in bone by increasing tumor area and osteoclast numbers. This process was associated with higher numbers of bone marrow adipocytes expressing IL-6 in direct vicinity to tumor cells. Inhibition of IL-6 or of downstream JAK2 blocked HFD-induced tumor progression. Furthermore, the phenotypic changes of melanoma cells triggered macrophage and osteoclast accumulation accompanied by increased osteopontin expression. Osteopontin triggered osteoclastogenesis and also exerted a positive feedback loop to tumor cells, which was abrogated in its absence. Metabolic stress by HFD promotes melanoma growth in the bone marrow by an increase in bone marrow adipocytes and IL-6-JAK2-osteopontin mediated activation of tumor cells and osteoclast differentiation.



FAU Authors / FAU Editors

Bäuerle, Tobias Prof. Dr.
Professur für Multimodale Bildgebung in der präklinischen Forschung
Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Chen, Guangliang
Lehrstuhl für Innere Medizin III
Meng, Xianyi
Juniorprofessur für Osteoimmunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III


External institutions
Fudan University / 复旦大学
Shanghai Jiao Tong University / 上海交通大学


How to cite

APA:
Chen, G., Luo, Y., Eriksson, D., Meng, X., Qian, C., Bäuerle, T.,... Bozec, A. (2016). High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6. Oncotarget, 7(18), 26653-69. https://dx.doi.org/10.18632/oncotarget.8474

MLA:
Chen, Guangliang, et al. "High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6." Oncotarget 7.18 (2016): 26653-69.

BibTeX: 

Last updated on 2019-25-04 at 14:57