Premium
Mechanical loading attenuates breast cancer‐associated bone metastasis in obese mice by regulating the bone marrow microenvironment
Author(s) -
Huang Menglu,
Liu Hong,
Zhu Lei,
Li Xinle,
Li Jie,
Yang Shuang,
Liu Daquan,
Song Xiaomeng,
Yokota Hiroki,
Zhang Ping
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30314
Subject(s) - bone marrow , osteolysis , breast cancer , medicine , endocrinology , tumor microenvironment , rankl , cancer , downregulation and upregulation , cancer research , bone metastasis , pathology , chemistry , receptor , surgery , activator (genetics) , biochemistry , gene
Breast cancer, a common malignancy for women, preferentially metastasizes to bone and obesity elevates the chance of its progression. While mechanical loading can suppress obesity and tumor‐driven osteolysis, its effect on bone‐metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity‐associated bone degradation in tumor‐invaded bone by regulating the fate of bone marrow‐derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X‐ray imaging, histology, cytology, and molecular analyses. Tumor inoculation to the tibia elevated body fat composition, osteolytic lesions, and tibia destruction, and these pathologic changes were stimulated by the high‐fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa‐B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C/enhancer‐binding protein alpha and proliferator‐activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1β. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor‐invaded bone by regulating the fate of bone marrow‐derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer‐associated bone metastasis, in particular for obese patients.