Impact of high fat diet and platelet activation on pre-metastatic niche formation

ABSTRACT: Metastasis involves dynamic interactions between tumor cells and the tumor microenvironment. Obesity has emerged as a significant contributor to tumor progression, particularly in breast cancer (BC). This study explores the impact of obesity on BC metastasis, focusing on the role of platelets and the formation of premetastatic niches (PMN). We found that high fat diet (HFD) leads to a basal pre-activation of platelets in circulation and endothelial cells in the lungs promoting the formation of “obese PMNs”. We observed that Fibronectin (FN) expression is upregulated both in platelets and endothelial cells in the lung of HFD-fed mice. We found that HFD led to enhanced interaction between platelets, tumor cells and endothelial cells within the PMN, increasing tumor cell homing and metastasis. Importantly, therapeutic interventions such as anti-platelet antibody administration or dietary restriction showed reduced metastatic cell homing and outgrowth. Moreover, FN blocking reduced tumor cell interaction with endothelial cell in HFD conditions. Importantly, analysis of coagulation parameters in triple negative BC patients before neoadjuvant treatment showed that subjects with reduced partial thromboplastin had a significantly shorter time to relapse. These findings highlight the significance of obesity-related factors and platelet-mediated coagulation in metastasis, suggesting potential therapeutic interventions and prognostic markers for BC patients.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Platelet, Blood

DISEASE(S): Breast Cancer

SUBMITTER: Pilar Ximenez-Embun  

LAB HEAD: Javier Munoz

PROVIDER: PXD051176 | Pride | 2025-03-22

REPOSITORIES: Pride