Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells
The lung is one of the deadliest sites of breast cancer metastasis, particularly for triple negative breast cancer (TNBC). We have previously shown that the lung produces several soluble factors that may enhance the metastatic behavior of TNBC, including E-, L-, and P-selectin. In this paper, we hyp...
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MDPI AG
2021-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1580 |
| _version_ | 1797511142708346880 |
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| author | Sami U. Khan Ying Xia David Goodale Gabriella Schoettle Alison L. Allan |
| author_facet | Sami U. Khan Ying Xia David Goodale Gabriella Schoettle Alison L. Allan |
| author_sort | Sami U. Khan |
| collection | DOAJ |
| description | The lung is one of the deadliest sites of breast cancer metastasis, particularly for triple negative breast cancer (TNBC). We have previously shown that the lung produces several soluble factors that may enhance the metastatic behavior of TNBC, including E-, L-, and P-selectin. In this paper, we hypothesize that lung-derived selectins promote TNBC metastatic behavior and may serve as a potential therapeutic target. Lungs were isolated from mice and used to generate lung-conditioned media (CM). Lung-derived selectins were immunodepleted and TNBC migration and proliferation were assessed in response to native or selectin-depleted lung-CM. A 3D ex vivo pulmonary metastasis assay (PuMA) was used to assess the metastatic progression of TNBC in the lungs of wild-type versus triple-selectin (ELP<sup>-/-</sup>) knockout mice. We observed that individual lung-derived selectins enhance in vitro migration (<i>p</i> ≤ 0.05), but not the proliferation of TNBC cells, and that ex vivo metastatic progression is reduced in the lungs of ELP<sup>-/-</sup> mice compared to wild-type mice (<i>p</i> ≤ 0.05). Treatment with the pan-selectin inhibitor bimosiamose reduced in vitro lung-specific TNBC migration and proliferation (<i>p</i> ≤ 0.05). Taken together, these results suggest that lung-derived selectins may present a potential therapeutic target against TNBC metastasis. Future studies are aimed at elucidating the pro-metastatic mechanisms of lung-derived selectins and developing a lung-directed therapeutic approach. |
| first_indexed | 2024-03-10T05:41:17Z |
| format | Article |
| id | doaj.art-68c564a2d0a04b208eb56853ed606e18 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:17Z |
| publishDate | 2021-10-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-68c564a2d0a04b208eb56853ed606e182023-11-22T22:30:20ZengMDPI AGBiomedicines2227-90592021-10-01911158010.3390/biomedicines9111580Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer CellsSami U. Khan0Ying Xia1David Goodale2Gabriella Schoettle3Alison L. Allan4Department of Anatomy & Cell Biology, Western University, London, ON N6A 3K7, CanadaRobarts Research Institute, Western University, London, ON N6A 3K7, CanadaLondon Health Sciences Centre, London Regional Cancer Program, London, ON N6A 5W9, CanadaSchulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, CanadaLondon Health Sciences Centre, London Regional Cancer Program, Departments of Oncology and Anatomy & Cell Biology, Lawson Health Research Institute, Western University, London, ON N6A 5W9, CanadaThe lung is one of the deadliest sites of breast cancer metastasis, particularly for triple negative breast cancer (TNBC). We have previously shown that the lung produces several soluble factors that may enhance the metastatic behavior of TNBC, including E-, L-, and P-selectin. In this paper, we hypothesize that lung-derived selectins promote TNBC metastatic behavior and may serve as a potential therapeutic target. Lungs were isolated from mice and used to generate lung-conditioned media (CM). Lung-derived selectins were immunodepleted and TNBC migration and proliferation were assessed in response to native or selectin-depleted lung-CM. A 3D ex vivo pulmonary metastasis assay (PuMA) was used to assess the metastatic progression of TNBC in the lungs of wild-type versus triple-selectin (ELP<sup>-/-</sup>) knockout mice. We observed that individual lung-derived selectins enhance in vitro migration (<i>p</i> ≤ 0.05), but not the proliferation of TNBC cells, and that ex vivo metastatic progression is reduced in the lungs of ELP<sup>-/-</sup> mice compared to wild-type mice (<i>p</i> ≤ 0.05). Treatment with the pan-selectin inhibitor bimosiamose reduced in vitro lung-specific TNBC migration and proliferation (<i>p</i> ≤ 0.05). Taken together, these results suggest that lung-derived selectins may present a potential therapeutic target against TNBC metastasis. Future studies are aimed at elucidating the pro-metastatic mechanisms of lung-derived selectins and developing a lung-directed therapeutic approach.https://www.mdpi.com/2227-9059/9/11/1580breast cancermetastasislung microenvironmentE-selectinL-selectinP-selectin |
| spellingShingle | Sami U. Khan Ying Xia David Goodale Gabriella Schoettle Alison L. Allan Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells Biomedicines breast cancer metastasis lung microenvironment E-selectin L-selectin P-selectin |
| title | Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells |
| title_full | Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells |
| title_fullStr | Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells |
| title_full_unstemmed | Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells |
| title_short | Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells |
| title_sort | lung derived selectins enhance metastatic behavior of triple negative breast cancer cells |
| topic | breast cancer metastasis lung microenvironment E-selectin L-selectin P-selectin |
| url | https://www.mdpi.com/2227-9059/9/11/1580 |
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