The disturbed iron phenotype of tumor cells and macrophages in renal cell carcinoma influences tumor growth

Matthias Schnetz, Julia K. Meier, Claudia Rehwald, Christina Mertens, Anja Urbschat, Elisa Tomat, Eman A. Akam, Patrick Baer, Frederik C. Roos, Bernhard Brüne, Michaela Jung

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Accumulating evidence suggests that iron homeostasis is disturbed in tumors. We aimed at clarifying the distribution of iron in renal cell carcinoma (RCC). Considering the pivotal role of macrophages for iron homeostasis and their association with poor clinical outcome, we investigated the role of macrophage-secreted iron for tumor progression by applying a novel chelation approach. We applied flow cytometry and multiplex-immunohistochemistry to detect iron-dependent markers and analyzed iron distribution with atomic absorption spectrometry in patients diagnosed with RCC. We further analyzed the functional significance of iron by applying a novel extracellular chelator using RCC cell lines as well as patient-derived primary cells. The expression of iron-regulated genes was significantly elevated in tumors compared to adjacent healthy tissue. Iron retention was detected in tumor cells, whereas tumor-associated macrophages showed an iron-release phenotype accompanied by enhanced expression of ferroportin. We found increased iron amounts in extracellular fluids, which in turn stimulated tumor cell proliferation and migration. In vitro, macrophage-derived iron showed pro-tumor functions, whereas application of an extracellular chelator blocked these effects. Our study provides new insights in iron distribution and iron-handling in RCC. Chelators that specifically scavenge iron in the extracellular space confirmed the importance of macrophage-secreted iron in promoting tumor growth.

Original languageEnglish (US)
Article number530
Issue number3
StatePublished - Mar 2020
Externally publishedYes


  • Chelation therapy
  • Iron
  • Macrophages
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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