Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion.

Bone Research
Yao FanHiroki Yokota

Abstract

Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium (CM) and fluid flow-treated conditioned medium (FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition (MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition (EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer (FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumor-induced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine. Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteoponti...Continue Reading

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Citations

Apr 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Di WuHiroki Yokota
Feb 16, 2021·Frontiers in Bioengineering and Biotechnology·Brandon D RiehlJung Yul Lim
Nov 10, 2020·Frontiers in Endocrinology·Manuel A RiquelmeJean X Jiang
Feb 7, 2021·Bone Research·Francisco ConceiçãoMeriem Lamghari

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Methods Mentioned

BETA
FRET
biosensor
ELISA
PCA

Software Mentioned

nRecon
NIS
MATLAB
CTan
Elements
ImageJ

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