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Following heme internalization, heme oxygenase-1 (HMOX-1) degrades heme to produce bilirubin, carbon monoxide, and ferrous ions, which inhibit the interactions of iron-binding proteins with iron response elements in FPN mRNA, thereby upregulating FPN expression and promoting tumor growth ( 5.2 Macrophage-mediated regulation of tumor cell ferroptosis Macrophages exhibit remarkable plasticity, changing their phenotype and functional spectrum in response to the microenvironment, thereby demonstrating the existence of heterogeneous subpopulations

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