Enzyme paves the way for the spread of cancer cells to bones
The spread of breast cancer to the bone affects approximately 85% of patients with advanced disease, and renders them largely untreatable. Researchers at BRIC, University of Copenhagen and the University of Sheffield UK have uncovered how a certain enzyme, produced by cancer cells in breast cancer patients, plays a central role in helping the spread of cancer cells to the bones. By blocking this enzyme, it is possible to prevent the cancer cells from growing in the bone and thereby save lives.
Microscope image of a breast cancer tumour showing hypoxic cells in green and DNA in blue. It is the hypoxic cells that produce lysyl oxidase.
“We have shown that cancer cells can affect the behavior of normal bone cells based on what they release into the body, and that this leads to changes in the bone that actually help the cancer cells to make a new home in the bone. By blocking these changes, we can prevent the cancer cells from growing in the bone. This approach could reduce associated complications and increase patient survival”, Lead researcher Janine Erler
LOX clears space for cancer cells in the bone tissue
The group of researchers lead by Janine Erler at BRIC at the University of Copenhagen and Alison Gartland at the University of Sheffield UK have discovered that certain types of breast cancer cells produce large amounts of the enzyme Lysyl oxidase (LOX), which helps the spread of cancer cells to the bone, by preparing the bone tissue for the arrival of cancer cells.
The study shows, that the LOX enzyme is produced in the cancer cells and released into the body where it works by altering the behaviour of normal non-cancerous bone cells. The alterations disrupt the delicate balance which protects the bone tissue and keeps it healthy, and in this way, the reprogramming of normal cells by cancer cells creates a microenvironment that helps the cancer cells to make a new home in the bone. Specifically, LOX released by breast cancer cells at the primary tumour, causes the formation of holes in the bone at distant sites to ‘clear space’ for the incoming cancer cells. This allows the breast cancer cells to take up residence in the bone, a place they would not normally be found. This study provides new understanding into how LOX produces these holes in the bone through a newly identified mechanism that causes a decrease in the activity of bone building cells, and an increase in the activity of bone destroying cells that normally work in balance in the bone.
Osteoporosis treatment may help breast cancer patients
The findings of the paper show that in certain breast cancer patients, there may be an added benefit of treating patients following diagnosis and surgery with bisphosphonates, an already approved drug in the clinic for the treatment of osteoporosis.
Microscope image of bone-destroying osteoclast cells generated by exposure to lysyl oxidase (red= cell body, blue= DNA)
“Bisphosphonates work by blocking the action of bone destroying cells (called osteoclasts). This then prevents cancer cell LOX from generating holes within the bone, and therefore reduces the ability of breast cancer cells to spread to the bone. Thus we propose that breast cancer patients whose tumours produce high levels of LOX should be considered for treatment with bisphosphonates. Such treatment may improve the survival of patients by reducing the likelihood of the cancer cells spreading to the bone.”, Thomas Cox, Assistant Professor in the Erler group
The results have just been published in the international journal Nature. The study was carried out at BRIC and University of Sheffield UK and funded by BRIC, Novo Nordisk Foundation (NNF), Danish Cancer Society, Lundbeck Foundation and Breast Cancer Campaign and Breakthrough Breast Cancer.
Contact: Associate Professor Janine Erler, Janine.erler@bric.ku.dk, Mobile phone: 20 34 11 06.
Contact
Associate Professor Janine Erler
Email: janine.erler@bric.ku.dk,
Mobile phone: +45 20 34 11 06.
Communications Officer Anne Rahbek-Damm
Email: anne.rahbek@bric.ku.dk,
Mobile phone: +45 21 28 85 41
Lysyl oxidase (LOX)
Lysyl oxidase (LOX) is an enzyme that alters the structural properties of tissue and is needed to maintain normal tissues in the body. While cells and non-aggressive cancer cells produce very low levels of LOX, aggressive cancer cells that tend to spread through the body produce high levels of LOX.
Original paper
Cox et al.: "The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase". Nature.