Impact of Anti-Angiogenic Treatment on Bone Vascularization in a Murine Model of Breast Cancer Bone Metastasis Using
Hao Xu1,2, Marie-Hélène Lafage-Proust3, Lamia Bouazza4
1Institute of Innovation Science and Technology, Shenyang University, Shenyang 110000, China.
Abstract:
Bone metastases are frequent complications of breast cancer, facilitating the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularization in response to tumor invasion under AAD is still partially understood. Therefore, the aim of this study was to explore the effect of AAD on experimental bone metastasis by analyzing the three-dimensional (3D) bone vasculature during metastatic formation and progression. Seventy-three eight-week-old female mice were treated with AAD (bevacizumab, vatalanib, or a combination of both drugs) or the vehicle (placebo) one day after injection with breast cancer cells. Mice were sacrificed eight or 22 days after tumor cell inoculation (time points T1 and T2, respectively). Synchrotron radiation microcomputed tomography (SR-μCT) was used to image bone and blood vessels with a contrast agent. Hence, 3D-bone and vascular networks were simultaneously visualized and quantitatively analyzed. At T1, the trabecular bone volume fraction was significantly increased (p < 0.05) in the combined AAD-treatment group, compared to the placebo- and single AAD-treatment groups. At T2, only the bone vasculature was reduced in the combined AAD-treatment group (p < 0.05), as judged by measurement of the blood vessel thickness. Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization.
Insights
Anti-angiogenic drugs (AAD) impact experimental breast cancer bone metastases. Early combined AAD treatment increased bone volume, while later treatment reduced bone vasculature thickness, affecting microvascularization structure.
Area of Science:
- Oncology
- Vascular Biology
- Skeletal Biology
Background:
- Bone metastases are common in breast cancer, leading to abnormal vascularization and bone destruction.
- Anti-angiogenic drugs (AAD) are explored for breast cancer bone metastasis treatment, but their effects on skeletal vascularization kinetics are not fully understood.
Purpose of the Study:
- To investigate the impact of AAD on experimental bone metastasis.
- To analyze three-dimensional (3D) bone vasculature during metastatic progression under AAD treatment.
Main Methods:
- Seventy-three mice with breast cancer bone metastasis were treated with AAD (bevacizumab, vatalanib, or combination) or placebo.
- Synchrotron radiation microcomputed tomography (SR-μCT) was used to visualize and quantify 3D bone and vascular networks at 8 and 22 days post-inoculation.
Main Results:
- At 8 days, combined AAD treatment significantly increased trabecular bone volume fraction compared to placebo or single AAD.
- At 22 days, combined AAD treatment reduced bone vasculature thickness, indicating an effect on microvascularization structure.
Conclusions:
- Combined AAD treatment may dampen early tumor-induced bone resorption without altering bone vessel organization.
- Later-stage combined AAD treatment affects the structural integrity of bone microvasculature in experimental bone metastasis.
