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The impact of a high fat diet and platelet activation on pre-metastatic niche formation
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Journal Article
The impact of a high fat diet and platelet activation on pre-metastatic niche formation
2025
Overview
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.
Previous work has identified a link between obesity and breast cancer metastasis. Here, using preclinical mouse models, the authors show that high-fat diet promotes platelet and endothelial cell activation in the lungs resulting in the development premetastatic niches, enhancing tumor cell homing and metastasis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/31
/ 13/51
/ 13/95
/ 14
/ 14/28
/ 14/5
/ 14/69
/ 38
/ 38/39
/ 42
/ 45
/ 49
/ 59
/ 64
/ 64/60
/ 96
/ Animals
/ Blood Platelets - metabolism
/ Diet
/ Diet, High-Fat - adverse effects
/ Endothelial Cells - metabolism
/ Endothelial Cells - pathology
/ Female
/ Homing
/ Humanities and Social Sciences
/ Humans
/ Lungs
/ Mice
/ Obesity
/ Science
/ Triple Negative Breast Neoplasms - blood
/ Triple Negative Breast Neoplasms - metabolism
/ Triple Negative Breast Neoplasms - pathology
/ Tumors
