180315 ONJCRI MR 0054 edit

Metastasis Research Laboratory

Laboratory overview

We have developed preclinical models of breast cancer metastasis that replicate the progress of the disease in patients. From these models, we have identified several genes that regulate the metastatic process. By investigating how these genes act to control metastasis, we can develop effective therapies that directly target these genes or other genes controlled by these metastasis regulators. Another important aspect of our research is to examine human breast cancer tissues for evidence that the gene identified in our preclinical models is also relevant in the human disease.

While over 80% of those diagnosed with breast cancer are now cured, this disease still kills more than eight Australians every day, largely due to the development of secondary cancers. Our research is aimed at reducing deaths from breast cancer. PROF. ROBIN ANDERSON, HEAD, METASTASIS RESEARCH LABORATORY
180315 ONJCRI MR 0106 180315 ONJCRI MR 0074 180315 ONJCRI MR 0096

Our focus

Metastasis Regulating Genes

We have shown that some of the genes that we have identified, including caveolin-1, microRNA-200 and BMP4, are able to suppress metastasis. For example, with BMP4, we have found that its metastasis suppressing activity is in part through the inhibition of G-CSF that controls the mobilisation and differentiation of neutrophils. In the presence of a tumour, the activity of neutrophils can be modified to support the spread of cancer cells to other organs, such as the lung. This has led to the demonstration that blocking the mobilisation of neutrophils can reduce metastasis in our preclinical models. We are now probing more deeply to understand how neutrophil function is altered by factors released from tumours and the relevance of this to patients with breast cancer.

Much of our research is focused on immune regulation of metastasis by the innate immune system, but some of the other genes that we have identified appear to act directly on the tumour cells to prevent their ability to metastasise.

Metastatic Dormancy

Breast cancer is noted for the long latency between diagnosis and development of secondary cancers, causing ongoing anxiety for the patient fearing a recurrence. We are investigating how tumour cells can disseminate from the primary tumour and remain alive but clinically undetectable for many years, and how they start expanding into life threatening cancers in some patients. We are seeking therapies that prevent the expansion of these dormant tumours.

Drug Discovery and Delivery

We collaborate closely with Dr Ian Street (WEHI) to screen for small molecules that can be developed into drugs to combat metastatic disease and with the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (Monash University) to improve drug delivery to tumours using nanoparticle technology.

Quick Facts

What is metastasis?

Metastasis is the process by which cancer cells spread from one organ to another, forming secondary tumours. Breast cancer commonly spreads to bone, liver, lung and brain.

What are neutrophils?

Neutrophils are a common type of white blood cell. They are an important part of the immune system and are found in sites of inflammation. They also contribute to the growth and spread of tumours.

What is nanoparticle technology? 

A nanometre is 1 billionth of a metre, hence nanoparticles are small enough to move through the bloodstream. Nanotechnology can deliver drugs to specific cells, such as tumour cells, reducing the chances of adverse reactions in the patient.

  1. Steigedal TS, Toraskar J, Redvers RP, Valla M, Magnussen SN, Bofin AM, Opdahl S, Lundgren S, Eckhardt BL, Lamar JM, Doherty J, Hynes RO, Anderson RL* and Svineng G* (2018). Nephronectin is correlated with poor prognosis in breast cancer and promotes metastasis via its integrin-binding motifs. *Co-senior authors. Neoplasia 20: 387-400.
  2. Martin, OA, Anderson, RL, Narayan, K and MacManus, MP (2017). Does the mobilization of circulating tumour cells during cancer therapy cause metastasis? Invited review for Nature Reviews Clinical Oncology 14: 32-44.
  3. Johnstone, CN, Smith, YE, Cao, Y, Burrows, AD, Cross, RSN, Ling, P, Redvers, RP, Doherty, JP, Eckhardt, BL, Natoli, A, Restall, C, Lucas, E, Pearson, H, Britt, KL, Rizzitelli, A, Li, J, Harmey, JH, Pouliot, N* and Anderson, RL* (2015). Functional and molecular characterization of mouse models of spontaneous metastatic breast cancer. Disease Models & Mechanisms 8: 237-251. *joint senior authors.
  4. Cao, Y, Slaney, CY, Bidwell, BN, Parker, BS, Johnstone, CJ, Rautela, J, Eckhardt, BL* and Anderson, RL* (2014). Bone morphogenetic protein-4 inhibits breast cancer metastasis by blocking myeloid derived suppressor cell activity. Cancer Research 74: 5091-5102. *joint senior authors.
  5. Swierczak, A, Cook, AD, Lenzo, JC, Restall, CM, Doherty, J, Anderson, RL* and Hamilton, JA* (2014) The promotion of breast cancer metastasis caused by inhibition of CSF-1R/CSF-1 signaling is blocked by targeting the G-CSF receptor.  Cancer Immunology Research 2: 765-776. *joint senior authors.
  6. Yu Miao, R, Eckhardt, BL, Cao, Y, Pasqualini, R, Argani, P, Arap, W, Ramsay, R* and Anderson, RL* (2013). Inhibition of Established Metastases by Targeted Drug Delivery via Cell Surface Associated GRP78. Clinical Cancer Research 19: 2107–2116.  *joint senior authors.
  7. Bidwell, BN, Slaney, Y, Withana, N, Forster, S, Cao, Y, Loi, S, Andrews, D., Mikeska, T, Mangan, NE., Samarajiwa, SA, de Weerd, NA, Gould, J, Argani, P, Moller, A, Smyth, MJ, Anderson, RL, Hertzog, P and Parker, BS (2012).  Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nature Medicine 18: 1224-1231.

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