The impact of a high fat diet and platelet activation on pre-metastatic niche formation
There is active crosstalk between tumor cells and the tumor microenvironment during metastatic progression, a process that is significantly affected by obesity, particularly in breast cancer. Here we analyze the impact of a high fat diet (HFD) on metastasis, focusing on the role of platelets in the formation of premetastatic niches (PMNs). We find that a HFD provokes pre-activation of platelets and endothelial cells, promoting the formation of PMNs in the lung. These niches are characterized by increased vascular leakiness, platelet activation and overexpression of fibronectin in both platelets and endothelial cells. A HFD promotes interactions between platelets, tumor cells and endothelial cells within PMNs, enhancing tumor cell homing and metastasis. Importantly, therapeutic interventions like anti-platelet antibody administration or a dietary switch reduce metastatic cell homing and outgrowth. Moreover, blocking fibronectin reduces the interaction of tumor cells with endothelial cells. Importantly, when coagulation parameters prior to neoadjuvant treatment are considered, triple negative breast cancer (TNBC) female patients with reduced Partial Thromboplastin time (aPTT) had a significantly shorter time to relapse. These findings highlight how diet and platelet activation in pre-metastatic niches affect tumor cell homing and metastasis, suggesting potential therapeutic interventions and prognostic markers for TNBC patients.
Authors
- Sara Sánchez‐Redondo (ORCID: https://orcid.org/0009-0000-5685-0467)
- Miguel Quintela-Fandiño (ORCID: https://orcid.org/0000-0003-1648-1964)
- Daniela F. Quail (ORCID: https://orcid.org/0000-0002-6969-3250)
- Pilar Ximénez‐Embún (ORCID: https://orcid.org/0000-0002-2582-9443)
- Héctor Peinado (ORCID: https://orcid.org/0000-0002-4256-3413)
- Sheri A. C. McDowell (ORCID: https://orcid.org/0000-0002-3155-8547)
- Gadea Mata (ORCID: https://orcid.org/0000-0002-5567-8463)
- Raúl Torres (ORCID: https://orcid.org/0000-0001-9606-0398)
- Diego Megı́as (ORCID: https://orcid.org/0000-0003-0755-0518)
- Manuel Pérez‐Martínez (ORCID: https://orcid.org/0000-0001-8839-6895)
- Marta Hergueta‐Redondo (ORCID: https://orcid.org/0000-0002-5244-9964)
- Sandra Rodríguez (ORCID: https://orcid.org/0000-0001-7221-3636)
- Begoña Hurtado (ORCID: https://orcid.org/0000-0002-8232-3238)
- Osvaldo Graña‐Castro (ORCID: https://orcid.org/0000-0003-1615-4242)
- Marina S. Mazariegos (ORCID: https://orcid.org/0000-0002-3298-9461)
- Vanesa Santos
- Lola Martínez
Institutions
- Universidad San Pablo CEU (ES)
- Universidad de La Rioja (ES)
- Lund University (SE)
- Spanish National Cancer Research Centre (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Madrid Health Service (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Centro de Investigación del Cáncer (ES)
- Hospital Universitario de Fuenlabrada (ES)
- Lund Science (Sweden) (SE)
- Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (ES)
- McGill University (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1038/s41467-025-57938-9
- Citations
- 8
- Primary Topic
- Inflammatory Biomarkers in Disease Prognosis
- Type
- article
- Field-Weighted Citation Impact
- 8.36
Funders
- Cancer Research UK
- Ministerio de Ciencia e Innovación
- Servier
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación