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Skeletal Loading Regulates Breast Cancer-associated Osteolysis in a Loading Intensity-dependent Fashion by Yao Fan; Aydin Jalali; Andy Chen; Xinyu Zhao; Shengzhi Liu; Meghana Teli; Yunxia Guo; Fangjia Li; Junrui Li; Amanda Siegel; Lianxiang Yang; Jing Liu; Sungsoo Na; Mangilal Agarwal; Alexander G. Robling; Harikrishna Nakshatri; Bai-Yan Li; Hiroki Yokota is a Medicine article available to read on EtoBox.

What is Skeletal Loading Regulates Breast Cancer-associated Osteolysis in a Loading Intensity-dependent Fashion about?

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 intensi

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Author
Yao Fan; Aydin Jalali; Andy Chen; Xinyu Zhao; Shengzhi Liu; Meghana Teli; Yunxia Guo; Fangjia Li; Junrui Li; Amanda Siegel; Lianxiang Yang; Jing Liu; Sungsoo Na; Mangilal Agarwal; Alexander G. Robling; Harikrishna Nakshatri; Bai-Yan Li; Hiroki Yokota
Publisher
Springer Science and Business Media LLC; Nature Publishing Group (ISSN 2095-4700)
Published
2020
Language
EN
Field
Medicine (Health Sciences)

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