Thomas R. Cox, Jan 2013
Scientists uncover a crucial link between tissue fibrosis and breast cancer metastasis
The spread of cancer around the body (metastasis) is the biggest cause of cancer related death in the world. The multiple processes which allow cancer cells to spread are highly complex and dynamic. Although it has long been known that tissue fibrosis and scarring can enhance primary tumour progression the underlying molecular mechanisms are still unclear.
The generation of environments that promote metastatic colonisation and growth of tumour cells is seen as a critical step in enabling metastasis. As such, understanding the events leading up to this will be crucial in aiding the development of new, effective cancer therapies.
Lysyl Oxidase (LOX) is an enzyme that is produced in response to tissue injury or chronic inflammation in our organs. It reacts to damage signals and “glues” collagen molecules together to form the scar-like structure. If this process is not carefully controlled, the result of can be a fibrotic environment.
In our work, we show that LOX is key to the development of tissue fibrosis and that its activity leads to the generation of environments that are favourable to the growth of metastastic tumour cells. We show that therapeutic targeting of LOX reduces not only the extent to which tissue fibrosis occurs, but also prevents this fibrosis-enhanced metastatic colonisation.
‘It is well-known that signals from fibrotic tissues can enhance tumour progression and metastasis, but the underlying mechanisms have remained unclear – Our new results provide insight into the link between fibrosis and cancer progression. Such a biological understanding is crucial if we are to develop effective therapies preventing tumour metastasis”, says PostDoc Thomas Cox from Janine Erler’s laboratory, who undertook the experimental investigation.
These findings provide an important link between extracellular matrix (ECM) homeostasis, tissue fibrosis, and cancer which has important clinical implications for both the treatment of fibrotic diseases and cancer.
Cox TR, Bird D, Baker AM, Barker HE, Ho MW-Y, Lang G, Erler JT. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res March 15, 2013 73; 1721. doi: 10.1158/0008-5472.CAN-12-2233
This study was supported by funding from Cancer Research UK C107/A10433, the Institute of Cancer Research, Biotech Research and Innovation Centre (BRIC) University of Copenhagen (UCPH), Hoffmann La Roche and a Hallas Møller Stipend from the Novo Nordisk Foundation.