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Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer
Breast cancer (BC) is the second-most common cause of brain metastases (BM) and BCBM patients have a reduced quality of life and a poor prognosis. Hyaluronan (HA), and in particular the hyaluronidase Hyal-1, has been already linked to the development of BCBM, and therefore presents an interesting op...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600690/ https://www.ncbi.nlm.nih.gov/pubmed/36291142 http://dx.doi.org/10.3390/cells11203275 |
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author | Hamester, Fabienne Stürken, Christine Legler, Karen Eylmann, Kathrin Möller, Katrin Roßberg, Maila Gorzelanny, Christian Bauer, Alexander T. Windhorst, Sabine Schmalfeldt, Barbara Laakmann, Elena Müller, Volkmar Witzel, Isabell Oliveira-Ferrer, Leticia |
author_facet | Hamester, Fabienne Stürken, Christine Legler, Karen Eylmann, Kathrin Möller, Katrin Roßberg, Maila Gorzelanny, Christian Bauer, Alexander T. Windhorst, Sabine Schmalfeldt, Barbara Laakmann, Elena Müller, Volkmar Witzel, Isabell Oliveira-Ferrer, Leticia |
author_sort | Hamester, Fabienne |
collection | PubMed |
description | Breast cancer (BC) is the second-most common cause of brain metastases (BM) and BCBM patients have a reduced quality of life and a poor prognosis. Hyaluronan (HA), and in particular the hyaluronidase Hyal-1, has been already linked to the development of BCBM, and therefore presents an interesting opportunity to develop new effective therapeutic options. HA metabolism was further discovered by the CRISPR/Cas9-mediated knockout of HYAL1 and the shRNA-mediated down-regulation of HA-receptor CD44 in the brain-seeking triple-negative breast cancer (TNBC) cell line MDA-MB-231-BR. Therefore, the impact of Hyal-1 on adhesion, disruption, and invasion through the brain endothelium, both in vitro and in vivo, was studied. Our analysis points out a key role of Hyal-1 and low-molecular-weight HA (LMW-HA) in the formation of a pericellular HA-coat in BC cells, which in turn promotes tumor cell adhesion, disruption, and migration through the brain endothelium in vitro as well as the extent of BM in vivo. CD44 knockdown in MDA-MB-231-BR significantly reduced the pericellular HA-coat on these cells, and, consequently, tumor cell adhesion and invasion through the brain endothelium. Thus, the interaction between Hyal-1-generated LMW-HA fragments and the HA-receptor CD44 might represent a potential target for future therapeutic options in BC patients with a high risk of cerebral metastases formation. |
format | Online Article Text |
id | pubmed-9600690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96006902022-10-27 Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer Hamester, Fabienne Stürken, Christine Legler, Karen Eylmann, Kathrin Möller, Katrin Roßberg, Maila Gorzelanny, Christian Bauer, Alexander T. Windhorst, Sabine Schmalfeldt, Barbara Laakmann, Elena Müller, Volkmar Witzel, Isabell Oliveira-Ferrer, Leticia Cells Article Breast cancer (BC) is the second-most common cause of brain metastases (BM) and BCBM patients have a reduced quality of life and a poor prognosis. Hyaluronan (HA), and in particular the hyaluronidase Hyal-1, has been already linked to the development of BCBM, and therefore presents an interesting opportunity to develop new effective therapeutic options. HA metabolism was further discovered by the CRISPR/Cas9-mediated knockout of HYAL1 and the shRNA-mediated down-regulation of HA-receptor CD44 in the brain-seeking triple-negative breast cancer (TNBC) cell line MDA-MB-231-BR. Therefore, the impact of Hyal-1 on adhesion, disruption, and invasion through the brain endothelium, both in vitro and in vivo, was studied. Our analysis points out a key role of Hyal-1 and low-molecular-weight HA (LMW-HA) in the formation of a pericellular HA-coat in BC cells, which in turn promotes tumor cell adhesion, disruption, and migration through the brain endothelium in vitro as well as the extent of BM in vivo. CD44 knockdown in MDA-MB-231-BR significantly reduced the pericellular HA-coat on these cells, and, consequently, tumor cell adhesion and invasion through the brain endothelium. Thus, the interaction between Hyal-1-generated LMW-HA fragments and the HA-receptor CD44 might represent a potential target for future therapeutic options in BC patients with a high risk of cerebral metastases formation. MDPI 2022-10-18 /pmc/articles/PMC9600690/ /pubmed/36291142 http://dx.doi.org/10.3390/cells11203275 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hamester, Fabienne Stürken, Christine Legler, Karen Eylmann, Kathrin Möller, Katrin Roßberg, Maila Gorzelanny, Christian Bauer, Alexander T. Windhorst, Sabine Schmalfeldt, Barbara Laakmann, Elena Müller, Volkmar Witzel, Isabell Oliveira-Ferrer, Leticia Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title | Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title_full | Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title_fullStr | Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title_full_unstemmed | Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title_short | Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer |
title_sort | key role of hyaluronan metabolism for the development of brain metastases in triple-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600690/ https://www.ncbi.nlm.nih.gov/pubmed/36291142 http://dx.doi.org/10.3390/cells11203275 |
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