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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
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Modeling Tumor: Lymphatic Interactions in Lymphatic Metastasis of Triple Negative Breast Cancer
Kyungmin Ji1, Zhiguo Zhao2, Mansoureh Sameni1
1Department of Pharmacology, Wayne State University, Detroit, MI 48201, USA.
Cancers
|December 10, 2021
Summary
Triple-negative breast cancer cells promote lymphatic metastasis by interacting with lymphatic endothelial cells. Understanding these interactions could lead to new therapies to prevent cancer spread.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Engineering
Background:
- Breast cancer metastasis to lymphatics is a key prognostic factor.
- Triple-negative breast cancer (TNBC) exhibits a high rate of lymphatic metastasis.
- Understanding TNBC cell and lymphatic endothelial cell (LEC) interactions is crucial for developing targeted therapies.
Purpose of the Study:
- To analyze the spatiotemporal interactions between human TNBC cells and human microvascular LECs.
- To investigate the mechanisms driving TNBC lymphatic metastasis using a novel 3D coculture model.
Main Methods:
- Utilized a novel microfluidic chamber for 3D coculture of TNBC and LECs.
- Employed live-cell imaging and secretomic analysis for non-invasive monitoring.
- Assessed spheroid growth, invasive outgrowths, and association with LEC networks over 4 days.
Main Results:
- TNBC:LEC cocultures formed larger 3D structures compared to monocultures.
- Increased multicellular invasive outgrowths from TNBC spheroids were observed.
- TNBC spheroids associated with LEC networks, and invasiveness increased in LEC-conditioned media.
Conclusions:
- Modeling TNBC and LEC spatiotemporal interactions reveals paracrine signaling pathways.
- These pathways are implicated in promoting lymphatic metastasis.
- Targeting identified paracrine signaling may offer a therapeutic strategy to reduce breast cancer lymphatic spread.
