ArticleOncotarget2016
High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.Frontiers in endocrinology · 2023Pooled it
- Comparative Proteomic Analysis of the Secretome of Control and BRAF/MEK Inhibitor-Resistant Melanoma Cells.Journal of proteome research · 2026Article
- Stress-induced IL-6 regulation in pediatric bone growth disorders: current insights and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Interplay of obesity and parasitic infection: current evidence of immunogenesis, tumorigenesis and leptin receptor involvement.Nutrition & metabolism · 2025Review
- Bone Marrow Adipocytes as Novel Regulators of Metabolic Homeostasis: Clinical Consequences of Bone Marrow Adiposity.Current obesity reports · 2025Review
- Exploring the multifaceted role of obesity in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Bone marrow microenvironment: roles and therapeutic implications in obesity-associated cancer.Trends in cancer · 2023Review
- Non-Invasive Characterization of Experimental Bone Metastasis in Obesity Using Multiparametric MRI and PET/CT.Cancers · 2022Article
- The Interplay between Tumour Microenvironment Components in Malignant Melanoma.Medicina (Kaunas, Lithuania) · 2022Review
- Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis.Frontiers in endocrinology · 2022Review
- Toward Marrow Adipocytes: Adipogenic Trajectory of the Bone Marrow Stromal Cell Lineage.Frontiers in endocrinology · 2022Review
- Xanthine dehydrogenase as a prognostic biomarker related to tumor immunology in hepatocellular carcinoma.Cancer cell international · 2021Article
- Novel approaches to target the microenvironment of bone metastasis.Nature reviews. Clinical oncology · 2021Review
- The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone.International journal of molecular sciences · 2021Review
- Melanoma Progression under Obesity: Focus on Adipokines.Cancers · 2021Review
- Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy.International journal of molecular sciences · 2021Review
- Worldwide flavor enhancer monosodium glutamate combined with high lipid diet provokes metabolic alterations and systemic anomalies: An overview.Toxicology reports · 2021Review
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.