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Matrix Microenvironment and Metastasis Laboratory

Laboratory Overview

Current therapies can successfully eradicate breast cancer in most patients when detected early. However, in a small proportion of patients the disease will recur and affect the normal functioning or vital organs such as the lungs, bone, liver and brain, leading to the patient’s demise. Unfortunately, current treatments are less effective against advanced breast cancer and, while extending life, they are rarely curative.

The Matrix Microenvironment and Metastasis Laboratory aims to understand how matrix proteins contribute to breast cancer metastasis. Our research focuses on understanding how interactions between cancer cells and the surrounding matrix enable cells to move away from the breast, spread through the blood vessels and prosper in distant organs. Our long term goal is to develop new approaches targeting these interactions, to stop metastasis and/or to identify patients likely to develop metastatic disease so that they can be treated earlier and more effectively.

The spread of breast cancer to distant organs (metastasis) is critically dependent on interactions between cancer cells and the surrounding matrix. This offers tremendous opportunities for the development of novel therapies to stop breast cancer in its track. Dr Normand Pouliot, Head, Matrix MIcroenvironment and Metastasis Laboratory

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Our focus

In collaboration with Australian and international researchers, our research team has developed clinically relevant mouse models of breast cancer metastasis that recapitulate the entire process of metastasis, from development of a primary tumour in the breast to the spontaneous spread of the disease to bone and brain, as seen in patients. Key projects in our laboratory make use of these models to identify “gene signatures” that can predict patients likely to develop metastases in the brain and other sites and to test the efficacy of various synthetic inhibitors and natural compounds against bone and brain metastasis. 

A particular focus of our laboratory is on evaluating whether potent integrin inhibitors derived from snake venom can be used to overcome resistance to current therapies or to convert aggressive breast cancers into a milder form of the disease that is more responsive to drugs already used in the clinic (i.e. anti-oestrogens).

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Quick facts

What is the matrix microenvironment?

The matrix microenvironment consists of a network of large proteins - called extracellular matrix (ECM) proteins - present in virtually all organs. ECM proteins help maintain the integrity and normal functioning of healthy organs. During cancer development, the expression of ECM proteins and their receptors on cancer cells (called integrins) is altered to promote survival, growth and homing of cancer cells to distant organs.

What are integrins?

Integrins are cell surface receptors that are used by cancer cells to attach to matrix proteins and to send signals controlling cancer cell survival, growth and movement.

  1. Carter R.Z., Micocci K.C., Natoli A., Redvers R.P., Paquet-Fifield S., Martin A.C., Denoyer D., Ling X., Kim S-H., Tomasin R., Selistre-de-Araújo H., Anderson R.L. and Pouliot N.  Tumour but not stromal expression of β3 integrin is essential, and is required early, for spontaneous dissemination of bone-metastatic breast cancer. The Journal of pathology 2015, 235(5):760-772.
  2. Johnstone C.N., Smith Y.E., Cao Y., Burrows A.D., Cross R.S., Ling X., Redvers R.P., Doherty J.P., Eckhardt B.L., Natoli A.L. Restall C., Lucas E., Pearson H.B., Britt K.L., Rizzitelli A., Li J., Harmey J.H., Pouliot N.* and Anderson R.L.* Functional and molecular characterisation of EO771.LMB, a new C57BL/6-derived model of spontaneously metastatic mammary cancer. Disease Models & Mechanisms 2015, 8(3):237-251.
  3. Denoyer D., Kusuma N., Burrows A., Ling X., Jupp L., Anderson R.L., Pouliot N.: Bone-derived soluble factors and laminin-511 cooperate to promote migration, invasion and survival of bone-metastatic breast tumor cells. Growth factors 2014, 32(2):63-73.
  4. Pouliot, N.,and Kusuma, N. Laminin-511: A multi-functional adhesion protein regulating cell migration, invasion and metastasis. Cell Adh. Migr. 2013, 7(1):142-9.
  5. Kusuma, N., Denoyer, D., Eble, J. A., Redvers, R. P., Parker, B. S., Pelzer, R., Anderson, R. L., and Pouliot, N. (2012) Integrin-dependent response to laminin-511 regulates breast tumor cell invasion and metastasis. Int J Cancer 2012, 130:555-66.

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