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S110 Dysregulated Iron Metabolism Mediated By Irp2 May Influence Lung Cancer Progression, Particularly In The Context Of Cigarette Smoke Exposure
  1. NA Ahmad1,
  2. JSM Moore1,
  3. KW Woolnough2,
  4. Ismail II2,
  5. MB Bedford1,
  6. UBN Naidu2,
  7. CT Tselepis1,
  8. AMT Turner2
  1. 1University of Birmingham, Birmingham, UK
  2. 2Heart of England NHS Foundation Trust, Birmingham, UK

Abstract

Background Iron is required for cell growth, and various cancers have been shown to proliferate more readily when iron replete. We have shown this previously in lung cancer and further demonstrated that this was reduced by either iron chelation or knockdown of IREB2, an iron regulatory gene. 1 Differences in iron content of bronchoalveolar lavage (BAL) fluid have been reported in smokers compared to non-smokers, 2 so we hypothesised that iron dysregulation might be an active mechanism of cancer progression in smokers.

Methods Two lung cancer cell lines were cultured with either ferrous (Fe2+) or ferric (Fe3+) forms of iron, or with cigarette smoke extract (CSE). Proliferation, apoptosis, necrosis and migration were assessed by BRDU assay, FACS and scratch wound assay respectively. Iron regulation was assessed by means of gene expression and Western blot for IREB2 (protein product IRP2), ferritin and transferrin receptor.

Resected lung cancers (n = 78) were stained for iron regulatory protein 2 (IRP2) and staining related to clinical features such as tumour size and survival.

Results Cancer cells proliferated more in the presence of ferrous iron or 5% CSE (p

Cancers staining positive for IRP2 tended to be larger (p = 0.045) and survival poorer (p = 0.079).

Conclusions Proliferation of cancer cells driven by iron dysregulation may be a clinically relevant mechanism in lung cancer, particularly in smokers.

References

  1. Kay et al, Thorax (2013) 68:A67-A68

  2. Nelson et al, AJRCCM (1996) 153: 1353–8

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