ArticleOncotarget2016
Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- A systematic review on leptin's role in defining cancer: special emphasis on immunomodulation, inflammation, and therapeutic interventions.Genes and immunity · 2025Pooled it
- Leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- Unveiling the link between chronic inflammation and cancer.Metabolism open · 2025Review
- Interactions between ferroptosis and tumour development mechanisms: Implications for gynaecological cancer therapy (Review).Oncology reports · 2025Review
- Combination of Thymoquinone and Intermittent Fasting as a Treatment for Breast Cancer Implanted in Mice.Plants (Basel, Switzerland) · 2023Article
- Role of Leptin and Adiponectin in Carcinogenesis.Cancers · 2023Review
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells.Acta biochimica et biophysica Sinica · 2022Article
- Review
- Chronic Leptin Treatment Induces Epithelial-Mesenchymal Transition in MCF10A Mammary Epithelial Cells.Journal of mammary gland biology and neoplasia · 2022Article
- Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer.NPJ breast cancer · 2021Article
- Leptin-Activity Modulators and Their Potential Pharmaceutical Applications.Biomolecules · 2021Review
- Review
- Inflammation-Induced Tumorigenesis and Metastasis.International journal of molecular sciences · 2021Review
- Obesity and Androgen Receptor Signaling: Associations and Potential Crosstalk in Breast Cancer Cells.Cancers · 2021Review
- Review
- New Actors Driving the Epithelial-Mesenchymal Transition in Cancer: The Role of Leptin.Biomolecules · 2020Review
- The Relationship between Leptin, the Leptin Receptor and FGFR1 in Primary Human Breast Tumors.Cells · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patient-derived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSC-mediated disease progression.
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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.