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Updated: Oct 1, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells
Ariana Joy L DeCastro1, Marina A Pranda1, Kelsey M Gray1
1Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States.
Abstract:
Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts aiming to help predict metastatic propensities to organ-specific sites in a clinical setting.
Insights
Triple negative breast cancer cells show distinct mechanical and migratory behaviors depending on their target metastatic site. Bone-seeking cells exhibit unique protrusive morphology and altered migration patterns, offering insights into organ-specific metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Cellular Mechanobiology
Background:
- Triple negative breast cancer (TNBC) preferentially metastasizes to bone and brain.
- Metastatic TNBC cells exhibit altered proteomic profiles and pathway activities.
- The microenvironment of metastatic sites influences cancer cell phenotypes.
Purpose of the Study:
- To investigate the mechanobiological phenotypes of TNBC cells conditioned for brain or bone metastasis.
- To compare the morphology, migration, and stiffness of parental, brain-seeking, and bone-seeking TNBC cells.
- To understand how microenvironmental cues influence TNBC cell behavior.
Main Methods:
- Utilized TNBC cells (MDA-MB-231) conditioned to metastasize to brain (MDA-BR) or bone (MDA-BO).
- Quantified cell morphology, migration dynamics, and cell stiffness.
- Assessed cell responses to substrates mimicking brain (fibronectin) and bone (collagen I) microenvironments.
- Analyzed focal adhesion area and density.
Main Results:
- Bone-seeking TNBC cells (MDA-BO) displayed a distinct protrusive morphology compared to parental (MDA-P) and brain-seeking (MDA-BR) cells.
- MDA-BO cells showed increased migration area on collagen I (bone mimic) versus fibronectin (brain mimic).
- Cell stiffness showed modest differences based on substrate coating, and confined migration was similar across cell types.
- MDA-BO cells exhibited larger focal adhesion area and density.
Conclusions:
- TNBC cells adapt distinct mechanobiological phenotypes based on their metastatic site.
- Bone-seeking TNBC cells possess unique migratory and morphological characteristics influenced by the bone microenvironment.
- These findings contribute to a quantitative profile of TNBC mechanobiology and may aid in predicting metastatic potential.
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