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Ex Vivo Model of Breast Cancer Cell Invasion in Live Lymph Node Tissue
Katerina Morgaenko1,2, Abhinav Arneja3, Alexander G Ball2,4
1Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
ACS Pharmacology & Translational Science
|March 20, 2025
Summary
This study introduces a new ex vivo model using live lymph node slices to study breast cancer cell invasion. The model reveals how cancer cells spread within lymph nodes and identifies key invasion pathways.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Lymph nodes (LNs) are critical sites for breast cancer metastasis.
- Understanding cancer cell invasion mechanisms within LNs is crucial for disease progression insights.
- Current in vivo models have limitations in isolating the tumor-draining lymph node (TDLN) microenvironment's specific effects.
Purpose of the Study:
- To develop and utilize a novel ex vivo model using live lymph node tissue slices to study breast cancer cell invasion.
- To investigate the spatial dynamics and preferential invasion routes of cancer cells within the lymph node microenvironment.
- To explore the role of specific chemokines and their receptors in cancer cell homing and invasion within lymph nodes.
Main Methods:
- Developed a 3D migration assay using live ex vivo lymph node tissue slices.
- Utilized BRPKp110 breast cancer cells to model invasion into naïve and premetastatic TDLNs.
- Analyzed cancer cell seeding, invasion, and spread within specific LN anatomical regions (SCS, cortex).
- Investigated the role of CXCR5/CXCL13 signaling in cancer cell invasion.
Main Results:
- Ex vivo LN slices successfully supported cancer cell seeding, invasion, and spread.
- Identified preferential cancer cell invasion into the subcapsular sinus (SCS) and cortex.
- Observed invasion towards immobilized CXCL13 and CCL1 chemokine gradients.
- CXCR5 was necessary for some invasion, but not solely sufficient to prevent spread towards CXCL13-rich areas.
- The model predicted lower invasion into premetastatic TDLNs, independent of chemokine secretion levels.
Conclusions:
- The developed ex vivo LN slice model provides a powerful platform for studying cancer cell invasion in a spatially organized microenvironment.
- This model allows for detailed analysis of cancer-immune interactions and the identification of factors influencing TDLN resistance to metastasis.
- Further research using this system can elucidate mechanisms of breast cancer metastasis and inform therapeutic strategies.
