Uncovering How Bone Metastasis Causes Anemia Through Cancer's Iron Hijacking

Researchers from Princeton University have uncovered a cellular mechanism explaining why bone metastasis often results in anemia in cancer patients. The study, published in the journal Cell, reveals that metastatic cancer cells in bone tissue hijack specialized iron-recycling cells, known as erythroblast island (EBI) macrophages. Under healthy conditions, these macrophages support red blood cell development by supplying iron; however, in the presence of cancer, tumor cells manipulate these macrophages, diverting their iron away from developing red blood cells and supporting tumor growth instead.

The research team, led by Yibin Kang and Yujiao Han, found that cancer cells effectively 'commandeer' EBI macrophages, depriving red blood cells of the iron necessary for their maturation, which contributes to anemia. Interestingly, the tumor cells also adapt by producing hemoglobin, mimicking red blood cells, to survive in the oxygen-poor environment of the bone. This process not only sustains the tumor but also creates a cycle of iron theft and red blood cell production disruption.

The study emphasizes the importance of viewing metastasis not only from the perspective of cancer 'seeds' but also by understanding the 'soil'—the surrounding environment that nurtures or inhibits cancer growth, as proposed by the 'seed and soil' hypothesis. Advanced cell-labeling and single-cell sequencing techniques allowed scientists to visualize and map the bone marrow microenvironment, uncovering how cancer cells recruit macrophages to support tumor expansion.

This discovery opens potential new avenues for therapies targeting the tumor's manipulation of iron metabolism in bone metastasis. Such strategies aim to not only slow or halt tumor progression but also to alleviate associated complications like anemia, significantly improving patient quality of life.

In addition to metastatic breast cancer, these findings could apply to other cancers that spread to bone, providing a broader understanding of how tumors interact with their microenvironment. This research underscores the significance of targeting both cancer cells and their supportive niches for more effective treatments.

Source: https://medicalxpress.com/news/2025-09-cancer-iron-theft-uncovers-bone.html