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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Autores principales:	Sami U. Khan, Ying Xia, David Goodale, Gabriella Schoettle, Alison L. Allan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	breast cancer metastasis lung microenvironment E-selectin L-selectin P-selectin Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/68c564a2d0a04b208eb56853ed606e18
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spelling	oai:doaj.org-article:68c564a2d0a04b208eb56853ed606e182021-11-25T16:49:15ZLung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells10.3390/biomedicines91115802227-9059https://doaj.org/article/68c564a2d0a04b208eb56853ed606e182021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1580https://doaj.org/toc/2227-9059The 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.Sami U. KhanYing XiaDavid GoodaleGabriella SchoettleAlison L. AllanMDPI AGarticlebreast cancermetastasislung microenvironmentE-selectinL-selectinP-selectinBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1580, p 1580 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer metastasis lung microenvironment E-selectin L-selectin P-selectin Biology (General) QH301-705.5
spellingShingle	breast cancer metastasis lung microenvironment E-selectin L-selectin P-selectin Biology (General) QH301-705.5 Sami U. Khan Ying Xia David Goodale Gabriella Schoettle Alison L. Allan Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells
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.
format	article
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
title	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_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_sort	lung-derived selectins enhance metastatic behavior of triple negative breast cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/68c564a2d0a04b208eb56853ed606e18
work_keys_str_mv	AT samiukhan lungderivedselectinsenhancemetastaticbehavioroftriplenegativebreastcancercells AT yingxia lungderivedselectinsenhancemetastaticbehavioroftriplenegativebreastcancercells AT davidgoodale lungderivedselectinsenhancemetastaticbehavioroftriplenegativebreastcancercells AT gabriellaschoettle lungderivedselectinsenhancemetastaticbehavioroftriplenegativebreastcancercells AT alisonlallan lungderivedselectinsenhancemetastaticbehavioroftriplenegativebreastcancercells
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Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells

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