Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells
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 extra...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.790410/full |
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| author | Ariana Joy L. DeCastro Marina A. Pranda Kelsey M. Gray John Merlo-Coyne Nathaniel Girma Madelyn Hurwitz Yuji Zhang Yuji Zhang Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka |
| author_facet | Ariana Joy L. DeCastro Marina A. Pranda Kelsey M. Gray John Merlo-Coyne Nathaniel Girma Madelyn Hurwitz Yuji Zhang Yuji Zhang Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka |
| author_sort | Ariana Joy L. DeCastro |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T03:23:11Z |
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| id | doaj.art-4090d4be282649ee995fceb4c1a86be4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T03:23:11Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-4090d4be282649ee995fceb4c1a86be42022-12-22T00:01:19ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-011010.3389/fcell.2022.790410790410Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor CellsAriana Joy L. DeCastro0Marina A. Pranda1Kelsey M. Gray2John Merlo-Coyne3Nathaniel Girma4Madelyn Hurwitz5Yuji Zhang6Yuji Zhang7Kimberly M. Stroka8Kimberly M. Stroka9Kimberly M. Stroka10Kimberly M. Stroka11Fischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Biology, University of Maryland, College Park, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Epidemiology and Public Health, University of Maryland, Baltimore, MD, United StatesMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, United StatesBiophysics Program, University of Maryland, College Park, MD, United StatesCenter for Stem Cell Biology and Regenerative Medicine, University of Maryland, Baltimore, MD, United StatesTriple 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.790410/fullcell migrationcell morphologytumor cellscell mechanical characterizationfocal adhesions |
| spellingShingle | Ariana Joy L. DeCastro Marina A. Pranda Kelsey M. Gray John Merlo-Coyne Nathaniel Girma Madelyn Hurwitz Yuji Zhang Yuji Zhang Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka Kimberly M. Stroka Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells Frontiers in Cell and Developmental Biology cell migration cell morphology tumor cells cell mechanical characterization focal adhesions |
| title | Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells |
| title_full | Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells |
| title_fullStr | Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells |
| title_full_unstemmed | Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells |
| title_short | Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells |
| title_sort | morphological phenotyping of organotropic brain and bone seeking triple negative metastatic breast tumor cells |
| topic | cell migration cell morphology tumor cells cell mechanical characterization focal adhesions |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.790410/full |
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