Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model

Background and purpose Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metas...

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Main Authors: Yun Zhang, Zhunyi Gao, Ziwei Qi, Jiahe Xu, Jiao Xue, Lujie Xiong, Junhui Wang, Yuhui Huang, Songbing Qin
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Cancer Biology & Therapy
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Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2025.2455756
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author Yun Zhang
Zhunyi Gao
Ziwei Qi
Jiahe Xu
Jiao Xue
Lujie Xiong
Junhui Wang
Yuhui Huang
Songbing Qin
author_facet Yun Zhang
Zhunyi Gao
Ziwei Qi
Jiahe Xu
Jiao Xue
Lujie Xiong
Junhui Wang
Yuhui Huang
Songbing Qin
author_sort Yun Zhang
collection DOAJ
description Background and purpose Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metastasis remains unclear.Methods We utilized a mouse model of breast cancer bone metastasis by intra-femoral injection of 4T1-luc breast tumor cells. The bone metastasis was treated by RT using various doses, timings, and modalities. Tumor growth was assessed through bioluminescence imaging, and lung metastases was quantified following lung tissue fixation. Flow cytometry was employed to analyze alterations in immune cell populations.Results Single high-dose RT suppressed tumor growth of bone metastases, but caused severe side effects. Conversely, fractionated RT mitigated tumor growth in bone metastases with fewer adverse effects. Fractioned RT initiated at the early stage of bone metastasis effectively inhibited tumor growth in the bone, suppressed secondary lung metastases, and prolonged mouse survival. In line with the known pro- and anti-metastatic effects of neutrophils and T cells in breast cancer, respectively, earlier fractioned RT consistently decreased the proportions of neutrophils while increased the proportions of T cells in both the bone and the lung tissues.Conclusion The data suggest that fractionated RT can inhibit the progression of early stage of bone metastasis and reduce secondary lung metastasis, leading to favorable outcomes. Therefore, these findings provide preclinical evidence to support the application of fractionated RT to treat patients with bone metastasis as earlier as possible.
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spelling doaj-art-5323ab3de0d4490daa2da865d70ddf532025-01-21T07:08:18ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2455756Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse modelYun Zhang0Zhunyi Gao1Ziwei Qi2Jiahe Xu3Jiao Xue4Lujie Xiong5Junhui Wang6Yuhui Huang7Songbing Qin8Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, State Key Laboratory of Radiation Medicine and Prevention, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, State Key Laboratory of Radiation Medicine and Prevention, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, State Key Laboratory of Radiation Medicine and Prevention, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaBackground and purpose Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metastasis remains unclear.Methods We utilized a mouse model of breast cancer bone metastasis by intra-femoral injection of 4T1-luc breast tumor cells. The bone metastasis was treated by RT using various doses, timings, and modalities. Tumor growth was assessed through bioluminescence imaging, and lung metastases was quantified following lung tissue fixation. Flow cytometry was employed to analyze alterations in immune cell populations.Results Single high-dose RT suppressed tumor growth of bone metastases, but caused severe side effects. Conversely, fractionated RT mitigated tumor growth in bone metastases with fewer adverse effects. Fractioned RT initiated at the early stage of bone metastasis effectively inhibited tumor growth in the bone, suppressed secondary lung metastases, and prolonged mouse survival. In line with the known pro- and anti-metastatic effects of neutrophils and T cells in breast cancer, respectively, earlier fractioned RT consistently decreased the proportions of neutrophils while increased the proportions of T cells in both the bone and the lung tissues.Conclusion The data suggest that fractionated RT can inhibit the progression of early stage of bone metastasis and reduce secondary lung metastasis, leading to favorable outcomes. Therefore, these findings provide preclinical evidence to support the application of fractionated RT to treat patients with bone metastasis as earlier as possible.https://www.tandfonline.com/doi/10.1080/15384047.2025.2455756Fractionated radiotherapybone metastasissecondary lung metastasisearly stageimmune cells
spellingShingle Yun Zhang
Zhunyi Gao
Ziwei Qi
Jiahe Xu
Jiao Xue
Lujie Xiong
Junhui Wang
Yuhui Huang
Songbing Qin
Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
Cancer Biology & Therapy
Fractionated radiotherapy
bone metastasis
secondary lung metastasis
early stage
immune cells
title Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
title_full Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
title_fullStr Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
title_full_unstemmed Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
title_short Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
title_sort fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model
topic Fractionated radiotherapy
bone metastasis
secondary lung metastasis
early stage
immune cells
url https://www.tandfonline.com/doi/10.1080/15384047.2025.2455756
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