Role of ferroptosis in nanofiber-induced carcinogenesis

Abstract

Biopersistent nanofibers with specified physical dimension are unexpected human carcinogens whether they are natural or synthetic.  Asbestos, a natural fibrous mineral, is classified as a definite human carcinogen (IARC Group 1) to cause malignant mesothelioma (MM) and lung cancer.  Multi-walled carbon nanotube of 50 nm-diameter was defined in 2014 as a possible carcinogen (IARC Group 2B) toward MM, fortunately with no authorized patients thus far.  Carcinogenic mechanism of asbestos has been a mystery for a long time.  It is now recognized that asbestos goes through lung parenchyma by collecting hemoglobin-derived iron to reach pleural cavity, which takes several decades.  Iron-loaded asbestos can induce oxidative damage directly to mesothelial cells, carcinogenesis-target cells lining somatic cavities.  Recently, it was clarified that surrounding stromal environment are as important for mesothelial carcinogenesis.  The novel concept here is ceaseless ferroptosis of macrophages, which forms a Fe(II)-dependent stromal mutagenic milieu indirectly for mesothelial cells and indeed is a revised understanding of frustrated phagocytosis.  Deposition of foreign materials eventually causes iron accumulation in situ due to the innate characteristic of preserving iron inside cells.  Nanofiber-induced carcinogenesis may be involved in other human carcinogenesis, including ovarian cancer.  Alternatively, iron excess can be an optimal target of cancer prevention and cancer treatment.

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