普林斯顿大学康毅滨团队近日取得一项新成果。经过不懈努力，他们的研究发现肿瘤劫持巨噬细胞供应铁以促进骨转移与贫血。这一研究成果发表在2025年9月3日出版的国际学术期刊《细胞》上。

研究人员发现，在小鼠模型中，一个特殊的VCAM1⁺CD163⁺CCR3⁺巨噬细胞群在骨转移生态位中高度富集，这些巨噬细胞通常是通过将铁转运到红母细胞而产生红细胞所必需的。肿瘤细胞劫持这些巨噬细胞的铁供应，减少红母细胞的铁供应，损害红细胞生成，并导致贫血。增加的铁供应使肿瘤细胞产生血红蛋白，以应对缺氧，模仿红母细胞。研究人员发现巨噬细胞在人类骨转移中具有类似的铁转运特征，并表明HBB表达升高与骨转移风险增加相关。这些发现证实了铁转运巨噬细胞是转移性骨生态位的重要组成部分，揭示了免疫细胞、金属代谢和肿瘤细胞可塑性在驱动转移和贫血中的重要相互作用。

据悉，骨髓既是造血的主要部位，也是转移的肥沃生态位。骨转移患者中常见贫血的发生机制尚不清楚。

附：英文原文

Title: Tumors hijack macrophages for iron supply to promote bone metastasis and anemia

Author: Yujiao Han, Hirak Sarkar, Zhan Xu, Sereno Lopez-Darwin, Yong Wei, Xiang Hang, Fengshuo Liu, Kimberley Tran, Wei Wang, Jennifer M. Miller, Christina J. DeCoste, Dylan S. Blohm, Robert L. Satcher, Xiang H.-F. Zhang, Yibin Kang

Issue&Volume: 2025-09-03

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 VCAM1+CD163+CCR3+ 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.

DOI: 10.1016/j.cell.2025.08.013

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00927-4