An international research team has identified what may be a critical molecule in the ability of tumours to metastasize -- or spread -- into bone.
The research, initiated at the University of Toronto and continued at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, found that a protein in bone called RANKL appears to communicate with a receptor in breast, prostate and skin cancer cells -- telling them to migrate. Moreover, a drug already known to block RANKL's activity may prevent cancers from spreading into the bone.
Roughly 120 years ago, scientists predicted that bone tissue might manufacture certain molecules that entice cancer cells to lodge there. More people die of metastases -- secondary tumours that develop elsewhere in the body -- than from their initial tumours and bone is particularly fertile "soil" for travelling cancer "seed" cells. It has been estimated that 70 per cent of patients with progressive breast cancer and 84 per cent of prostate cancer patients develop bone metastases.
D. Holstead Jones, a former post-doctoral fellow in Professor Josef Penninger's laboratory of medical biophysics and immunology at U of T, is the lead author of the paper, which appears in the March 30 issue of the journal Nature. The team also included researchers from the University of Western Ontario's Department of Physiology and Pharmacology. Josef Penninger is currently the director of the IMBA in Vienna, where the project is being continued.
Jones and her colleagues show that RANKL, a cytokine protein which is produced at high levels in bone marrow, acts on breast, prostate and skin cancer cells through the RANK receptor. Over the past few years, Penninger's lab had determined that RANKL is essential in both bone breakdown and in controlling the growth of cells that form a lactating mammary gland. Putting these two discoveries together, the team decided to study the link between breast cancer and bone metastases and the RANKL system.