Tissue Stiffening is Key to Aggressive Cancers
19 November 2009 - Scientists have identified an enzyme that is crucial for turning abnormal but non-malignant breast tissue into tumours, according to study published in Cell online.
The supportive tissue surrounding breast cancer cells is shaped differently to healthy tissue as well as stiffer and more fibrous, but until now scientists have not known what was causing these modifications.
A research team - led by the University of California, San Francisco, and including ICR scientist Janine Erler - found the enzyme lysyl oxidase (LOX) changed the structure of collagen, the major component of this supportive tissue, in a process known as cross-linking.
In experimental models, higher levels of LOX increased the levels of collagen in mammary glands, made the tissue stiffer and correlated with a higher frequency of tumours invading the breast tissue.
Blocking LOX using chemicals or an antibody reduced the number of cross-links in mammary gland collagen and led to fewer, smaller and less aggressive tumours.
“Our study shows that stiffening of the breast tissue controlled by enzymes such as LOX is a key factor in cancer development, suggesting these enzymes are a promising candidate drug target,” Dr Erler says. “The enzyme triggers a clear physical change in breast tissue and if we could stop this happening we expect it would slow the growth of any cancers that did develop and make them easier to eradicate.”
Dr Erler’s previous studies have already highlighted the importance of LOX in cancer spread, showing that it promotes metastasis by sending out signals that prepare a new area of the body for invasion. The new study shows that LOX is also crucial for primary tumour progression, and that cells within the connective tissue – not just the tumours themselves – express LOX.
