Thomas R. Cox, Sep 2015
I have been invited to give a seminar at the Graduate School of Medicine, Chiba University in Japan on 17th September 2015.
My talk will be titled:
“Fibrosis, Cancer and the Pre-Metastatic Niche:
Implications for Lysyl Oxidase”
The metastasis of solid tumours remains one of the highest causes of mortality for cancer patients. Understanding the mechanisms by which primary tumours are able to colonise distant secondary organs to generate overt metastases remains a key challenge in cancer research.
The dynamic and reciprocal interaction between tumour cells and their microenvironment is crucial to many stages of development and progression. During progression and metastasis, the tumour extracellular matrix (ECM) is continuously remodelled both biochemically and biomechanically, feeding back onto tumour cells to enhance progression. Furthermore, the ability of tumour cells to alter ECM remodelling and re-program host cells at distant pre-metastatic sites prior to their arrival is a chilling reality.
We have shown that Lysyl Oxidase (LOX), a secreted ECM remodelling enzyme is critical to both breast and colorectal cancer progression. LOX expression at primary tumours leads to changes in ECM biochemistry and biomechanics, altering Src, FAK and NFATc1 signalling to drive progression and metastasis across multiple models. LOX activity modulates tissue stiffness leading to enhanced tumour growth, angiogenesis and metastasis. LOX is also crucially involved in pre-metastatic niche formation in multiple tissues including the lung, liver and bone, through altering recruitment and activation of host cells. The mechanisms contributing to primary tumour development, metastatic progression and tissue fibrosis share many commonalities and we have also shown that LOX is also critical to the onset and development of tissue fibrosis and that LOX activity is key to establishing a milieu within fibrosing tissues that is favourable to colonisation and growth of metastatic tumour cells.
Together our data suggest that targeting LOX is a highly attractive target for blocking the pro-tumourigenic and pro-metastatic changes in the ECM during cancer progression and metastasis across multiple solid tumours.
Read more about Chiba University here