ArticleBreast cancer research and treatment2015
Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production.
Article in Breast cancer research and treatment, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Signals from the Adipose Microenvironment and the Obesity-Cancer Link-A Systematic Review.Cancer prevention research (Philadelphia, Pa.) · 2017Pooled it
- Low Testosterone in Men With Type 2 Diabetes: The Role of Estrogen Excess and Aromatase Activity.Clinical endocrinology · 2026Article
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Host-microbiome interactions in breast cancer progression and treatment response.Frontiers in medicine · 2026Review
- Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.Frontiers in immunology · 2026Article
- Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer.Frontiers in immunology · 2026Review
- Is Adipose Tissue Inflammation the Culprit of Obesity-Associated Comorbidities?Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Translating Metabolic Interventions into Breast Cancer Therapy: A Comprehensive Review.Life (Basel, Switzerland) · 2025Review
- Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases.Bioactive materials · 2024Article
- Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.Advances in experimental medicine and biology · 2024Review
- Update on Adipose Tissue and Cancer.Endocrine reviews · 2023Article
- Hot Spots and Trends in the Relationship between Cancer and Obesity: A Systematic Review and Knowledge Graph Analysis.Life (Basel, Switzerland) · 2023Review
- The pleiotropic roles of adipocyte secretome in remodeling breast cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Article
- Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors.Breast cancer : basic and clinical research · 2022Article
- Impact of intestinal dysbiosis on breast cancer metastasis and progression.Frontiers in oncology · 2022Review
- Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis.NPJ breast cancer · 2021Article
- Mechanistic Insights into the Link between Obesity and Prostate Cancer.International journal of molecular sciences · 2021Review
- The role of immune dysfunction in obesity-associated cancer risk, progression, and metastasis.Cellular and molecular life sciences : CMLS · 2021Review
- Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Obesity is associated with a worse breast cancer prognosis, particularly in estrogen receptor alpha (ERα) positive, postmenopausal patients. We hypothesized that this is mediated in part by an elevation in breast cancer cell cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production that results in greater local pre-adipocyte aromatase expression. We utilized an in vitro model of the obese patient's tumor microenvironment in which cultured MCF-7 breast cancer cells and pre-adipocytes were exposed to pooled serum from obese (OB; BMI ≥ 30.0 kg/m(2)) or normal weight (N; BMI 18.5-24.9 kg/m(2)) postmenopausal women. Exposure to OB versus N sera significantly increased MCF-7 cell COX-2 expression and PGE2 production. Pre-adipocyte aromatase expression was 89 % greater following culture in conditioned media (CM) from MCF-7 cells exposed to OB versus N sera (OB-CM and N-CM, respectively), a difference nullified by MCF-7 cell treatment with the COX-2 inhibitor celecoxib. Previous analysis of the sera revealed significantly higher interleukin-6 (IL-6) concentrations in the OB versus N samples. Depletion of IL-6 from the sera neutralized the difference in pre-adipocyte aromatase expression stimulated by OB-CM versus N-CM. Finally, CM from pre-adipocyte/MCF-7 cell co-cultures exposed to OB sera stimulated greater MCF-7 and T47D breast cancer cell ERα activity and proliferation in comparison to N sera. This study indicates that obesity-associated systemic IL-6 indirectly enhances pre-adipocyte aromatase expression via increased breast cancer cell PGE2 production. Investigation regarding the efficacy of a COX-2 inhibitor/aromatase inhibitor combination therapy in the obese postmenopausal patient population is warranted.
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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.