Healthy cells defend against breast cancer

Healthy mammary epithelial cells act as the immune system’s second line of defence, secreting a protein – known for its role in response to inflammation – to target breast cancer cells

[caption id="" align="alignnone" width="200" caption="Stained sections of control (a) and IL-25–treated tumours (b). Control sample shows actively growing tumour cells (arrows); in the IL-25–treated sample, the tumour was completely regressed Credit Saori Furuta"][/caption]

Researchers from Lawrence Berkeley National Laboratory discovered that normal breast cancer cells maintain the health and integrity of tissue surrounding them by secreting interleukin 25 – IL25. IL25 was shown to be highly toxic to breast cancer cells – which have an abundance of exposed IL25 receptors – but harmless to normal breast cells.

“We found that normal breast cells provide an innate defence mechanism against cancer by producing IL25 to actively and specifically kill breast cancer cells,” said Mina Bissell who led the research. “This suggests that IL25 receptor signalling may provide a new therapeutic target for the treatment of breast cancer.”

Researchers showed that conditioned medium, taken from normal mammary epithelial cells while in the process of forming acini in a 3D lamin-rich extracellular matrix culture, can make the malignant phenotype of breast cancer behave as if they were normal breast cells.

“We hypothesised that such a complex pheonotypical reversion is likely the result of multiple signalling factors that in combination allow cancer cells to form quiescent acinar-like structures,” said Bissell.

Researchers used solubility and size-fractionation of the conditioned medium to reveal that the most potent tumour cell-killing activity took place in the 10-50 kiloDalton range, and mass spectrometry to reveal IL25.

“We analysed randomised cohorts of breast biopsy samples and found that 20% of the breast cancer samples tested were IL25 receptor-positive,” said co-lead author Saori Furuta. “Importantly these IL25 receptor-positive tumours were highly invasive and correlated to poor clinical outcome in patients. We believe that in the future the IL25 receptor will serve as a novel therapeutic marker for breast cancer diagnosis and treatment.”

The team are now looking at five other proteins they discovered being secreted by normal developing breast cells. These proteins stop the growth of cancer cells, rather than killing them, but researchers are investigating whether a combination of these other proteins with IL25 could be an effective therapy against some forms of aggressive breast and other cancers.