ECM Remodelling during Cancer Progression

The extracellular matrix (ECM) is one of the most important regulators of cellular and tissue function in the body. The ECM is known to play a critical role in driving cancer progression, and yet we lack knowledge of how ECM is altered during tumour progression to promote cancer metastasis. We have found that an enzyme secreted by tumour and stromal cells called lysyl oxidase (LOX) is responsible for altering the ECM at primary and metastatic sites to greatly enhance metastasis. LOX is an amine oxidase that catalyses the crosslinking of collagens and elastin in the ECM. LOX activity alters the structural and biochemical properties of the ECM, to drive cell proliferation, invasion and angiogenesis. Importantly, LOX modifies pre-metastatic tissue microenvironments prior to tumour cell arrival, enhancing metastatic colonisation and outgrowth. We are expanding our studies to further investigate how ECM is remodelled during cancer progression and how this impacts on cell behaviour to drive metastasis.