Breast cancer cells suppress immune defence pathways in order to spread to bone

Project Description

Breast cancer is extremely common, effecting 1 in 9 Australian women. For patients that develop metastatic spread to other organs, the options for therapy are limited and rarely curative.

It is therefore critical to determine the mechanisms of breast cancer spread to common tissues such as lung and bone to allow the identification of specific molecular targets that may enable the development of more effective therapies. We are specifically interested in the role of the immune system in the metastatic process.

For this reason, we have utilised a unique mouse model of breast cancer that closely mimics the human disease and has a competent immune system. Using this model, we have recently discovered that tumour cells growing in bone suppress genes involved in immune response and a significant number of these genes were members of the Type I interferon (IFN) pathway.

Type I IFNs were originally identified for their anti-viral properties and have recently been implicated in the detection and elimination of tumours. The loss of this pathway in tumour cells that have spread to bone suggests that the Type I IFNs may have suppressive effects on metastasis, possibly by stimulating a tumour-specific immune response.

To test this, we aim to alter the production of IFN to test if this can suppress breast cancer spread in the mouse model. We have restored this pathway in breast cancer cells and have proven that this leads to a significant reduction in breast cancer spread and extended mouse survival.

We have also shown that members of this pathway are also lost in the human disease supporting clinical relevance of our findings. Our future work will determine if the mechanism of metastasis suppression by the Type I IFN pathway is through stimulation of an anti-tumour immune response.

Final Lay Report  

Year

2009-2010

Researchers

Dr Belinda Parker, Prof Paul Hertzog

Funding Body

Cancer Council Research Grant

Institution

Peter MacCallum Cancer Centre

Funding

$99,750 in 2009 and $97,150 in 2010

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