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1篇 您的检索式:作者名="Alexander G.Robling"
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1Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion显示文摘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 tumorinduced 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 osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.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 2020Bone Research2020,8,2:4
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