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Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells

Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, w...

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Autores principales: Keller, Florian, Bruch, Roman, Clauder, Franziska, Hafner, Mathias, Rudolf, Rüdiger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225072/
https://www.ncbi.nlm.nih.gov/pubmed/34073955
http://dx.doi.org/10.3390/cells10061304
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author Keller, Florian
Bruch, Roman
Clauder, Franziska
Hafner, Mathias
Rudolf, Rüdiger
author_facet Keller, Florian
Bruch, Roman
Clauder, Franziska
Hafner, Mathias
Rudolf, Rüdiger
author_sort Keller, Florian
collection PubMed
description Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic cleavage and extracellular matrix components on BSP expression and distribution in cell culture models. Therefore, MDA-MB-231 human breast cancer cells were kept in 2D and 3D spheroid cultures and exposed to basement membrane extract in the presence or absence of matrix metalloproteinase 9 or the non-polar protease, dispase. Confocal imaging of immunofluorescence samples stained with different antibodies against human BSP demonstrated a strong inducing effect of basement membrane extract on anti-BSP immunofluorescence. Similarly, protease incubation led to acute upregulation of anti-BSP immunofluorescence signals, which was blocked by cycloheximide, suggesting de novo formation of BSP. In summary, our data show that extracellular matrix components play an important function in regulating BSP expression and hint at mechanisms for the formation of bone-associated metastasis in breast cancer that might involve local control of BSP levels by extracellular matrix degradation and release of growth factors.
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spelling pubmed-82250722021-06-25 Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells Keller, Florian Bruch, Roman Clauder, Franziska Hafner, Mathias Rudolf, Rüdiger Cells Article Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic cleavage and extracellular matrix components on BSP expression and distribution in cell culture models. Therefore, MDA-MB-231 human breast cancer cells were kept in 2D and 3D spheroid cultures and exposed to basement membrane extract in the presence or absence of matrix metalloproteinase 9 or the non-polar protease, dispase. Confocal imaging of immunofluorescence samples stained with different antibodies against human BSP demonstrated a strong inducing effect of basement membrane extract on anti-BSP immunofluorescence. Similarly, protease incubation led to acute upregulation of anti-BSP immunofluorescence signals, which was blocked by cycloheximide, suggesting de novo formation of BSP. In summary, our data show that extracellular matrix components play an important function in regulating BSP expression and hint at mechanisms for the formation of bone-associated metastasis in breast cancer that might involve local control of BSP levels by extracellular matrix degradation and release of growth factors. MDPI 2021-05-24 /pmc/articles/PMC8225072/ /pubmed/34073955 http://dx.doi.org/10.3390/cells10061304 Text en © 2021 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
Keller, Florian
Bruch, Roman
Clauder, Franziska
Hafner, Mathias
Rudolf, Rüdiger
Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title_full Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title_fullStr Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title_full_unstemmed Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title_short Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells
title_sort extracellular matrix components regulate bone sialoprotein expression in mda-mb-231 breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225072/
https://www.ncbi.nlm.nih.gov/pubmed/34073955
http://dx.doi.org/10.3390/cells10061304
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