Back to Search
Start Over
Triple-Negative Breast Cancer-Derived Extracellular Vesicles Promote a Hepatic Pre-metastatic Niche via a Cascade of Microenvironment Remodeling
- Source :
- Molecular Cancer Research. :OF1-OF15
- Publication Year :
- 2023
- Publisher :
- American Association for Cancer Research (AACR), 2023.
-
Abstract
- Patients with triple-negative breast cancer (TNBC) often develop metastases in visceral organs including the liver, but the detailed molecular mechanisms of TNBC liver metastasis is not clearly understood. In this study, we tried to dissect the process of pre-metastatic niche formation in the liver by using patient-derived xenograft (PDX) models of TNBC with different metastatic propensity. RNA sequencing of TNBC PDX models that successfully metastasized to liver showed upregulation of the Cx3cr1 gene in the liver microenvironment. In syngeneic breast cancer models, the Cx3cr1 upregulation in liver preceded the development of cancer cell metastasis and was the result of recruitment of CX3CR1-expressing macrophages. The recruitment was induced by the CX3CL1 production from the liver endothelial cells and this CX3CL1–CX3CR1 signaling in the pre-metastatic niche resulted in upregulation of MMP9 that promoted macrophage migration and cancer cell invasion. In addition, our data suggest that the extracellular vesicles derived from the breast cancer cells induced the TNFα expression in liver, which leads to the CX3CL1 upregulation. Lastly, the plasma CX3CL1 levels in 155 patients with breast cancer were significantly associated with development of liver metastasis. Implications: Our data provides previously unknown cascades regarding the molecular education of pre-metastatic niche in liver for TNBC.
- Subjects :
- Cancer Research
Oncology
Molecular Biology
Subjects
Details
- ISSN :
- 15573125 and 15417786
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Research
- Accession number :
- edsair.doi...........8912d8faca088c3b5f1e0802a6664fb6