@article{204246, keywords = {Primary}, author = {Yujiao Han and Hirak Sarkar and Zhan Xu and Sereno Lopez-Darwin and Yong Wei and Xiang Hang and Fengshuo Liu and Kimberley Tran and Wei Wang and Jennifer Miller and Christina DeCoste and Dylan Blohm and Robert Satcher and Xiang Zhang and Yibin Kang}, title = {Tumors hijack macrophages for iron supply to promote bone metastasis and anemia.}, abstract = {
Bone marrow is both a primary site for hematopoiesis and a fertile niche for metastasis. The mechanism of the common occurrence of anemia among patients with bone metastasis remains poorly understood. Here, we show that a specialized population of VCAM1CD163CCR3 macrophages, normally essential for erythropoiesis by transporting iron to erythroblasts, are highly enriched in the bone metastatic niche in mouse models. Tumor cells hijack these macrophages for iron supply, reducing iron availability for erythroblasts, impairing erythropoiesis, and contributing to anemia. Increased iron supply enables tumor cells to produce hemoglobin in response to hypoxia, mimicking erythroblasts. We identify macrophages with similar iron-transporting features in human bone metastases and show that elevated HBB expression correlates with increased risk of bone metastasis. These findings establish iron-transporting macrophages as an essential component of the metastatic bone niche, revealing a critical interplay between immune cells, metal metabolism, and tumor cell plasticity in driving metastasis and anemia.
}, year = {2025}, journal = {Cell}, volume = {188}, pages = {6335-6354.e26}, month = {10/2025}, issn = {1097-4172}, doi = {10.1016/j.cell.2025.08.013}, language = {eng}, }