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The impact of a high fat diet and platelet activation on pre-metastatic niche formation

Hergueta-Redondo, Marta ; Sánchez-Redondo, Sara ; Hurtado, Begoña ; Santos, Vanesa ; Pérez-Martínez, Manuel ; Ximénez- Embún, Pilar ; McDowell, Sheri A.C. ; Mazariegos, Marina S. LU orcid ; Mata, Gadea and Torres-Ruiz, Raúl , et al. (2025) In Nature Communications 16(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
16
issue
1
article number
2897
publisher
Nature Publishing Group
external identifiers
  • scopus:105001702410
  • pmid:40175356
ISSN
2041-1723
DOI
10.1038/s41467-025-57938-9
language
English
LU publication?
yes
id
52f153a5-3964-4b2c-81da-6e490c5bc3c6
date added to LUP
2025-08-06 11:13:40
date last changed
2025-08-20 12:30:22
@article{52f153a5-3964-4b2c-81da-6e490c5bc3c6,
  abstract     = {{<p>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.</p>}},
  author       = {{Hergueta-Redondo, Marta and Sánchez-Redondo, Sara and Hurtado, Begoña and Santos, Vanesa and Pérez-Martínez, Manuel and Ximénez- Embún, Pilar and McDowell, Sheri A.C. and Mazariegos, Marina S. and Mata, Gadea and Torres-Ruiz, Raúl and Rodríguez-Perales, Sandra and Martínez, Lola and Graña-Castro, Osvaldo and Megias, Diego and Quail, Daniela and Quintela-Fandino, Miguel and Peinado, Héctor}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The impact of a high fat diet and platelet activation on pre-metastatic niche formation}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-57938-9}},
  doi          = {{10.1038/s41467-025-57938-9}},
  volume       = {{16}},
  year         = {{2025}},
}