Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish
Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/995 |
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| author | Udhayakumar Gopal Jerry D. Monroe Amarnath S. Marudamuthu Salma Begum Bradley J. Walters Rodney A. Stewart Chad W. Washington Yann Gibert Marcus A. Zachariah |
| author_facet | Udhayakumar Gopal Jerry D. Monroe Amarnath S. Marudamuthu Salma Begum Bradley J. Walters Rodney A. Stewart Chad W. Washington Yann Gibert Marcus A. Zachariah |
| author_sort | Udhayakumar Gopal |
| collection | DOAJ |
| description | Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish <i>casper</i> (<i>roy</i>-/-; <i>nacre</i>-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples. |
| first_indexed | 2024-03-11T05:40:37Z |
| format | Article |
| id | doaj.art-3de66fd41a6d40558852f49a35b9b4fa |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:40:37Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3de66fd41a6d40558852f49a35b9b4fa2023-11-17T16:27:48ZengMDPI AGCells2073-44092023-03-0112799510.3390/cells12070995Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in ZebrafishUdhayakumar Gopal0Jerry D. Monroe1Amarnath S. Marudamuthu2Salma Begum3Bradley J. Walters4Rodney A. Stewart5Chad W. Washington6Yann Gibert7Marcus A. Zachariah8Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Otolaryngology-Head and Neck Surgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USANeurosurgical Medical Clinic, 3750 Convoy Street, Suite 301, San Diego, CA 92111, USALeptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish <i>casper</i> (<i>roy</i>-/-; <i>nacre</i>-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples.https://www.mdpi.com/2073-4409/12/7/995triple-negative breast cancerzebrafishleptomeningeal diseasexenograftdoxorubicin |
| spellingShingle | Udhayakumar Gopal Jerry D. Monroe Amarnath S. Marudamuthu Salma Begum Bradley J. Walters Rodney A. Stewart Chad W. Washington Yann Gibert Marcus A. Zachariah Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish Cells triple-negative breast cancer zebrafish leptomeningeal disease xenograft doxorubicin |
| title | Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish |
| title_full | Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish |
| title_fullStr | Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish |
| title_full_unstemmed | Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish |
| title_short | Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish |
| title_sort | development of a triple negative breast cancer leptomeningeal disease model in zebrafish |
| topic | triple-negative breast cancer zebrafish leptomeningeal disease xenograft doxorubicin |
| url | https://www.mdpi.com/2073-4409/12/7/995 |
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