Lean adipocytes promote ferroptosis in breast cancer cells

A study by Curtin et al., published in Science, investigated how adipocyte secretions may affect breast cancer progression. The researchers compared breast cancer cells exposed to secretions from lean or obese adipocytes and found enrichment of ferroptosis-related transcripts with lean adipocyte secretions. Cell death increased under lean-secretome conditions and could be rescued with ferroptosis inhibitors.

The lean secretome was also associated with higher intracellular ferrous iron and increased expression of HMOX1 and CD71 in cancer cells. In mice bearing E0771 tumours, the ferroptosis marker 4-HNE was elevated in tumours from lean mice. Treatment with a ferroptosis inhibitor reduced 4-HNE and increased tumour growth. The authors identify the adipocyte-derived oxylipin 9S-HODE as a mediator of this effect. These cell and animal findings suggest a mechanism linking adipocyte state with breast cancer progression; they do not establish that 9S-HODE or ferroptosis manipulation is effective or safe in people.