Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells
To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confoc...
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MDPI AG
2020-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/797 |
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| author | Lanpeng Chen Maciej Boleslaw Olszewski Marianna Kruithof-de Julio B. Ewa Snaar-Jagalska |
| author_facet | Lanpeng Chen Maciej Boleslaw Olszewski Marianna Kruithof-de Julio B. Ewa Snaar-Jagalska |
| author_sort | Lanpeng Chen |
| collection | DOAJ |
| description | To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial−mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDH<sup>hi</sup> cancer stem-like cells (CSCs) and ALDH<sup>low</sup> non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation. |
| first_indexed | 2024-03-12T08:07:53Z |
| format | Article |
| id | doaj.art-703d7d2771f84cc5a17f9f8d7f3e8938 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:07:53Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-703d7d2771f84cc5a17f9f8d7f3e89382023-09-02T19:20:56ZengMDPI AGCells2073-44092020-03-019479710.3390/cells9040797cells9040797Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer CellsLanpeng Chen0Maciej Boleslaw Olszewski1Marianna Kruithof-de Julio2B. Ewa Snaar-Jagalska3Institute of Biology, Leiden University, 2311 EZ Leiden, The NetherlandsDepartment of Molecular Biology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, PolandDepartment for BioMedical Research, Bern University, 3008 Bern, SwitzerlandInstitute of Biology, Leiden University, 2311 EZ Leiden, The NetherlandsTo visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial−mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDH<sup>hi</sup> cancer stem-like cells (CSCs) and ALDH<sup>low</sup> non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation.https://www.mdpi.com/2073-4409/9/4/797zebrafish xenograft modelprostate cancercell plasticity |
| spellingShingle | Lanpeng Chen Maciej Boleslaw Olszewski Marianna Kruithof-de Julio B. Ewa Snaar-Jagalska Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells Cells zebrafish xenograft model prostate cancer cell plasticity |
| title | Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells |
| title_full | Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells |
| title_fullStr | Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells |
| title_full_unstemmed | Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells |
| title_short | Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells |
| title_sort | zebrafish microenvironment elevates emt and csc like phenotype of engrafted prostate cancer cells |
| topic | zebrafish xenograft model prostate cancer cell plasticity |
| url | https://www.mdpi.com/2073-4409/9/4/797 |
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