Scientists at The Institute of Cancer Research, London, discovered that the enzyme, called LOXL2, facilitates the process of tumour cell invasion, a key stage in cancer progression.
Their study, published in Molecular Cancer Research, found that blocking the LOXL2 enzyme significantly slowed the spread of breast cancer in mice, suggesting it could be a promising target for new drugs designed to stop cancer from spreading around the body.
For cancers to spread through the body, they need ‘scaffolding’ for tumour cells to move along. Cells called fibroblasts, as well as the proteins they secrete such as collagen, are a key part of this scaffolding. In non-cancerous tissue, they provide a structure for healthy organs to develop and heal. Cancer cells can hijack this process by recruiting fibroblasts from the host tissue. These cancer-associated fibroblasts (CAFs) become activated by the tumour cells and produce increased amounts of collagen and other components to create scaffolding that facilitates tumour cell invasion - and the new research helps explain how they do this.
Dr Holly Barker, Postdoctoral Training Fellow at The Institute of Cancer Research (ICR) and first author on the study, said: “The LOXL2 enzyme is secreted by tumours and plays a vital role in activating cancer-associated fibroblasts, leading to the spread of cancer. We found that these activated fibroblasts also secrete more LOXL2, thereby activating more fibroblasts in a chain reaction which allows cancers to survive, spread and invade healthy tissue. Our results strongly support the targeting of LOXL2 to stop the spread of cancer throughout the body.”
The study found that blocking LOXL2 not only reduced the number of activated CAFs, but also reduced their ability to produce a stiff scaffold. When LOXL2 is present the tumours recruit more healthy fibroblasts, turning them into cancer-associated fibroblasts that contribute to the production of a stiff matrix, enabling cancer cells to spread.
This study adds to the body of evidence supporting the development of LOXL2 inhibitors. There are currently LOXL2 inhibitors in Phase II cancer trials in the US and Dr Barker has high hopes for their future:
“This is a really exciting area of research, as it could provide a way to stop cancers from spreading around the body. LOXL2 is important during development, but expression of LOXL2 is low in most healthy adult tissues so LOXL2 inhibitors shouldn’t have serious side-effects. As our latest study shows just how important LOXL2 is for the spread of tumours, I believe LOXL2 inhibitors have a promising future ahead.”