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Breast cancer–secreted factors perturb murine bone growth in regions prone to metastasis

MPG-Autoren
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Liu,  Chuang
Mason Dean, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Moreno-Jiménez,  Inés
Amaia Cipitria, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Tang,  Tengteng
Wolfgang Wagermaier, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Wagermaier,  Wolfgang
Wolfgang Wagermaier, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Dean,  Mason N.
Mason Dean, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Fratzl,  Peter
Peter Fratzl, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Chiou, A. E., Liu, C., Moreno-Jiménez, I., Tang, T., Wagermaier, W., Dean, M. N., et al. (2021). Breast cancer–secreted factors perturb murine bone growth in regions prone to metastasis. Science Advances, 7(12): eabf2283. doi:10.1126/sciadv.abf2283.


Zitierlink: https://hdl.handle.net/21.11116/0000-0008-3CD7-3
Zusammenfassung
Breast cancer frequently metastasizes to bone, causing osteolytic lesions. However, how factors secreted by primary tumors affect the bone microenvironment before the osteolytic phase of metastatic tumor growth remains unclear. Understanding these changes is critical as they may regulate metastatic dissemination and progression. To mimic premetastatic bone adaptation, immunocompromised mice were injected with MDA-MB-231–conditioned medium [tumor-conditioned media (TCM)]. Subsequently, the bones of these mice were subjected to multiscale, correlative analysis including RNA sequencing, histology, micro–computed tomography, x-ray scattering analysis, and Raman imaging. In contrast to overt metastasis causing osteolysis, TCM treatment induced new bone formation that was characterized by increased mineral apposition rate relative to control bones, altered bone quality with less matrix and more carbonate substitution, and the deposition of disoriented mineral near the growth plate. Our study suggests that breast cancer–secreted factors may promote perturbed bone growth before metastasis, which could affect initial seeding of tumor cells.