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Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer

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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.

In: CELLS-BASEL, Vol. 11, No. 20, 3275, 18.10.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hamester, F, Stürken, C, Legler, K, Eylmann, K, Möller, K, Roßberg, M, Gorzelanny, C, Bauer, AT, Windhorst, S, Schmalfeldt, B, Laakmann, E, Müller, V, Witzel, I & Oliveira-Ferrer, L 2022, 'Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer', CELLS-BASEL, vol. 11, no. 20, 3275. https://doi.org/10.3390/cells11203275

APA

Hamester, F., Stürken, C., Legler, K., Eylmann, K., Möller, K., Roßberg, M., Gorzelanny, C., Bauer, A. T., Windhorst, S., Schmalfeldt, B., Laakmann, E., Müller, V., Witzel, I., & Oliveira-Ferrer, L. (2022). Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer. CELLS-BASEL, 11(20), [3275]. https://doi.org/10.3390/cells11203275

Vancouver

Hamester F, Stürken C, Legler K, Eylmann K, Möller K, Roßberg M et al. Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer. CELLS-BASEL. 2022 Oct 18;11(20). 3275. https://doi.org/10.3390/cells11203275

Bibtex

@article{ffdf0e9dec014e1383a99e744a104f93,
title = "Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer",
abstract = "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.",
keywords = "Humans, Brain Neoplasms/metabolism, Cell Line, Tumor, Hyaluronic Acid/metabolism, Hyaluronoglucosaminidase/genetics, Quality of Life, RNA, Small Interfering, Triple Negative Breast Neoplasms/pathology",
author = "Fabienne Hamester and Christine St{\"u}rken and Karen Legler and Kathrin Eylmann and Katrin M{\"o}ller and Maila Ro{\ss}berg and Christian Gorzelanny and Bauer, {Alexander T.} and Sabine Windhorst and Barbara Schmalfeldt and Elena Laakmann and Volkmar M{\"u}ller and Isabell Witzel and Leticia Oliveira-Ferrer",
year = "2022",
month = oct,
day = "18",
doi = "10.3390/cells11203275",
language = "English",
volume = "11",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "20",

}

RIS

TY - JOUR

T1 - Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer

AU - Hamester, Fabienne

AU - Stürken, Christine

AU - Legler, Karen

AU - Eylmann, Kathrin

AU - Möller, Katrin

AU - Roßberg, Maila

AU - Gorzelanny, Christian

AU - Bauer, Alexander T.

AU - Windhorst, Sabine

AU - Schmalfeldt, Barbara

AU - Laakmann, Elena

AU - Müller, Volkmar

AU - Witzel, Isabell

AU - Oliveira-Ferrer, Leticia

PY - 2022/10/18

Y1 - 2022/10/18

N2 - 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.

AB - 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.

KW - Humans

KW - Brain Neoplasms/metabolism

KW - Cell Line, Tumor

KW - Hyaluronic Acid/metabolism

KW - Hyaluronoglucosaminidase/genetics

KW - Quality of Life

KW - RNA, Small Interfering

KW - Triple Negative Breast Neoplasms/pathology

U2 - 10.3390/cells11203275

DO - 10.3390/cells11203275

M3 - SCORING: Journal article

C2 - 36291142

VL - 11

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 20

M1 - 3275

ER -