ArticleBreast cancer research : BCR2019
Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP).
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 131 citations in OpenAlex.
- Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy.Journal of the National Cancer Institute · 2021Trial
- An Exploratory Study on the Interrelation of Breast Cancer Molecular Phenotypes with Breast Cancer-Associated Adipose Tissues (BCAATs), Neoadjuvant, and Adjuvant Therapies: A Focus on Prognosis and Survival.Medical sciences (Basel, Switzerland) · 2026Article
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- 3D bioprinting for cancer modeling and drug screening.Biomarker research · 2026Review
- Body Mass Index Does Not Predict High Miller-Payne Response to Neoadjuvant Chemotherapy in Stage II-III Breast Cancer: A Single-Center Retrospective Cohort Study of 647 Patients.Journal of clinical medicine · 2026Article
- The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.Cancer communications (London, England) · 2026Review
- Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.International journal of molecular sciences · 2025Review
- Adipocytes Promote Cisplatin Resistance through Secreting A1BG and Regulating NAMPT/PARP1 Axis-Mediated DNA Repair in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigation into the sensitivity of adipocytes mediated by the major vault protein (MVP) to chemotherapy for triple-negative breast cancer.Translational cancer research · 2025Article
- Plasma exosomes from individuals with type 2 diabetes drive breast cancer aggression in patient-derived organoids.Communications biology · 2025Article
- The recent progress of tumor cell-derived exosomes in the pathogenesis, diagnosis and therapeutic strategies of tumors.Journal of translational medicine · 2025Review
- Lovastatin inhibits adipocyte-associated increased proliferation, EMT and aggressiveness of breast cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC).Journal of translational medicine · 2025Article
- Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.NPJ breast cancer · 2025Article
- Vault Particles in Cancer Progression, Multidrug Resistance, and Drug Delivery: Current Insights and Future Applications.International journal of molecular sciences · 2025Review
- Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.Cellular & molecular biology letters · 2025Review
- The role of the tumor microenvironment in HNSCC resistance and targeted therapy.Frontiers in immunology · 2025Review
- Obesity promotes immunotherapy efficacy by up-regulating the glycolytic-mediated histone lactacylation modification of CD8+ T cells.Frontiers in pharmacology · 2025Article
- Editorial: Molecular markers for pancreatic cancers: new technologies and applications in the clinical practice.Frontiers in oncology · 2025Article
- Valosin-containing protein (VCP), a component of tumor-derived extracellular vesicles, impairs the barrier integrity of brain microvascular endothelial cells.BBA advances · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionClinical studies suggest that obesity, in addition to promoting breast cancer aggressiveness, is associated with a decrease in chemotherapy efficacy, although the mechanisms involved remain elusive. As chemotherapy is one of the main treatments for aggressive or metastatic breast cancer, we investigated whether adipocytes can mediate resistance to doxorubicin (DOX), one of the main drugs used to treat breast cancer, and the mechanisms associated.
methodsWe used a coculture system to grow breast cancer cells with in vitro differentiated adipocytes as well as primary mammary adipocytes isolated from lean and obese patients. Drug cellular accumulation, distribution, and efflux were studied by immunofluorescence, flow cytometry, and analysis of extracellular vesicles. Results were validated by immunohistochemistry in a series of lean and obese patients with cancer.
resultsAdipocytes differentiated in vitro promote DOX resistance (with cross-resistance to paclitaxel and 5-fluorouracil) in a large panel of human and murine breast cancer cell lines independently of their subtype. Subcellular distribution of DOX was altered in cocultivated cells with decreased nuclear accumulation of the drug associated with a localized accumulation in cytoplasmic vesicles, which then are expelled into the extracellular medium. The transport-associated major vault protein (MVP), whose expression was upregulated by adipocytes, mediated both processes. Coculture with human mammary adipocytes also induced chemoresistance in breast cancer cells (as well as the related MVP-induced DOX efflux) and their effect was amplified by obesity. Finally, in a series of human breast tumors, we observed a gradient of MVP expression, which was higher at the invasive front, where tumor cells are at close proximity to adipocytes, than in the tumor center, highlighting the clinical relevance of our results. High expression of MVP in these tumor cells is of particular interest since they are more likely to disseminate to give rise to chemoresistant metastases.
conclusionsCollectively, our study shows that adipocytes induce an MVP-related multidrug-resistant phenotype in breast cancer cells, which could contribute to obesity-related chemoresistance.
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