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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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Hauptverfasser: Keller, Florian (VerfasserIn) , Bruch, Roman (VerfasserIn) , Clauder, Franziska (VerfasserIn) , Hafner, Mathias (VerfasserIn) , Rudolf, Rüdiger (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 May 2021
In: Cells
Year: 2021, Jahrgang: 10, Heft: 6, Pages: 1-15
ISSN:2073-4409
DOI:10.3390/cells10061304
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cells10061304
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2073-4409/10/6/1304
Volltext
Verfasserangaben:Florian Keller, Roman Bruch, Franziska Clauder, Mathias Hafner, Rüdiger Rudolf

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520 |a 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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