Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Type 1 interferons as potent suppressors of breast cancer metastasis to bone (#190)

Jai Rautela 1 , Clare Slaney 1 , Belinda Parker 1
  1. Sir Peter MacCallum Cancer Institute, East Melbourne, Vic, Australia

Breast cancer is the most commonly diagnosed non-skin cancer among Western women. Early diagnosis and treatment result in good long-term survival, however, women that succumb usually do so due to the cancer metastasising to vital organs. Approximately 70% of breast cancer cases metastasise to the bone, creating painful and untreatable loss of bone density leading to fractures and paralysis.

Recent work in the laboratory has shown that breast cancer cells spread to bone by suppressing tumour cell induced type I interferon (IFN) signalling.  Restoration of this signalling in tumour cells by enforced expression of the master regulator interferon regulatory factor 7 (Irf7) significantly reduces metastasis to bone by stimulating anti-tumour immune responses. 

Our current work will explore the direct role of tumour cell IFN in regulating metastatic spread and its' potential as a therapeutic for patients likely to develop bone metastasis.  We will do this by enforced expression of two type I IFNs (IFN alpha and IFN beta) in tumour cells, to examine the impact on bone metastasis in the 4T1.2 syngeneic model.  Additionally, we will treat mice bearing 4T1.2 tumours systemically with type I IFNs to assess the therapeutic benefit.  Our preliminary experiments show that IFN significantly reduces metastasis to bone.  We will now explore the best therapeutic window for treatment by mimicking the adjuvant and metastatic treatment setting in mouse models of metastasis. 

This will allow assessment of the future utility of IFN therapies in breast cancer patients.