Cancer Cells Usurp Iron-Recycling Macrophages in Bone Metastasis, leading to Anemia

In a groundbreaking development, researchers led by scientists at Princeton University have uncovered a significant aspect of metastatic breast cancer. They found that cancer cells commandeer specialized erythroblast island (EBI) macrophages, which are responsible for recycling iron in the bone, disrupting the process and leading to complications such as anemia.

Bone marrow, which is both a primary site for hematopoiesis and a fertile niche for metastasis, plays a crucial role in this discovery. The presence of bone metastases not only lures these macrophages but also diverts their iron away from red blood cells, impairing their development and contributing to anemia.

This hijacking of EBI macrophages by tumor cells for iron supply is a new research direction, shifting the focus from the "seeds" of cancer to the "soil" in which it grows within a metastatic organ site. The "seed and soil hypothesis," first proposed more than a century ago by British surgeon Stephen Paget, is being revisited by the team.

The findings have been extended to other major cancer types, with similar iron metabolism features observed in a subset of macrophages in human bone metastases across multiple cancer types. This suggests that the mechanism of anemia among patients with bone metastasis could be a common occurrence.

In an effort to understand and treat this condition, specialists investigating anemia caused by cancer cells in metastatic bone tumors are typically oncologists and hematologists working within multidisciplinary oncology centers. These experts combine research and patient care to understand and treat blood-related complications in cancer.

Preventing the tumor's rerouting of EBI macrophages or restoring their function could offer an effective therapeutic strategy to alleviate anemia and inhibit tumor progression in bone metastasis. The team's research aims to help uncover how to slow down bone metastasis and improve the quality of life and survival for patients.

Interestingly, tumor cells have been found to adapt by mimicking red blood cells, producing hemoglobin under the guidance of a blood-cell transcription factor called GATA1. This "red blood cell mimicry" allows the tumor to thrive in the bone's oxygen-poor environment, protecting cancer cells from stress and helping them survive.

Understanding the mechanisms driving cancer-associated anemia and developing targeted treatments are crucial for improving both life quality and survival. The new discoveries made by Kang and his team promise to open up new avenues for research and potential treatments for patients with bone metastasis.

Cancer Cells Usurp Iron-Recycling Macrophages in Bone Metastasis, leading to Anemia