Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential
Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7087 |
| _version_ | 1797605174624124928 |
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| author | Bai Zhang Xueyi Li Kai Tang Ying Xin Guanshuo Hu Yufan Zheng Keming Li Cunyu Zhang Youhua Tan |
| author_facet | Bai Zhang Xueyi Li Kai Tang Ying Xin Guanshuo Hu Yufan Zheng Keming Li Cunyu Zhang Youhua Tan |
| author_sort | Bai Zhang |
| collection | DOAJ |
| description | Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength. The selected cells up-regulated the genes related to brain metastasis and exhibited an enhanced ability to transmigrate through the blood–brain barrier. In the soft microenvironments that mimicked brain tissue, these cells had elevated adhesion and survival ability. Further, tumor cells selected by brain endothelium adhesion expressed higher levels of <i>MUC1</i>, <i>VCAM1</i>, and <i>VLA-4</i>, which were relevant to breast cancer brain metastasis. In summary, this study provides the first piece of evidence to support that the adhesion of circulating tumor cells to the brain endothelium selects the cells with enhanced brain metastasis potential. |
| first_indexed | 2024-03-11T04:57:23Z |
| format | Article |
| id | doaj.art-ab8bf0b496874423873aa46fc4327803 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:57:23Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ab8bf0b496874423873aa46fc43278032023-11-17T19:35:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248708710.3390/ijms24087087Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis PotentialBai Zhang0Xueyi Li1Kai Tang2Ying Xin3Guanshuo Hu4Yufan Zheng5Keming Li6Cunyu Zhang7Youhua Tan8The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, ChinaTumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength. The selected cells up-regulated the genes related to brain metastasis and exhibited an enhanced ability to transmigrate through the blood–brain barrier. In the soft microenvironments that mimicked brain tissue, these cells had elevated adhesion and survival ability. Further, tumor cells selected by brain endothelium adhesion expressed higher levels of <i>MUC1</i>, <i>VCAM1</i>, and <i>VLA-4</i>, which were relevant to breast cancer brain metastasis. In summary, this study provides the first piece of evidence to support that the adhesion of circulating tumor cells to the brain endothelium selects the cells with enhanced brain metastasis potential.https://www.mdpi.com/1422-0067/24/8/7087endothelial adhesionbiomechanicsmechanobiologyfluid shear stressbrain metastasis |
| spellingShingle | Bai Zhang Xueyi Li Kai Tang Ying Xin Guanshuo Hu Yufan Zheng Keming Li Cunyu Zhang Youhua Tan Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential International Journal of Molecular Sciences endothelial adhesion biomechanics mechanobiology fluid shear stress brain metastasis |
| title | Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential |
| title_full | Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential |
| title_fullStr | Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential |
| title_full_unstemmed | Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential |
| title_short | Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential |
| title_sort | adhesion to the brain endothelium selects breast cancer cells with brain metastasis potential |
| topic | endothelial adhesion biomechanics mechanobiology fluid shear stress brain metastasis |
| url | https://www.mdpi.com/1422-0067/24/8/7087 |
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