A protein that is active in growing embryos but not normal adult tissue, has also been found in various types of cancer. Now a new US study suggests it may switch on metastasis, the ability of cancer cells to spread and form new tumors in other parts of the body. The researchers say it offers a new target for anti-cancer treatments that block the protein without harming healthy cells.

Metastasis is responsible for 90% of cancer-related deaths, highlighting a need for treatments that stop cancer cells migrating, note principal investigator Thomas Kipps, from University of California – San Diego (UCSD), and colleagues, in the 15 June online issue of the journal Cancer Research.

They report how they found a link between the protein ROR1 (short for Receptor-tyrosine-kinase-like Orphan Receptor 1) and a process called EMT (epithelial-mesenchymal transition), which occurs during early embryo development when cells migrate to make new organs,and during cancer metastasis.

In 2012, the team reported for the first time in PLoS ONE, that the gene that codes for ROR1 is expressed during embryo development and different types of cancer but not normal adult tissue.

In that study they also showed how silencing the gene stopped human breast cancer cells from growing and surviving.

Now in this latest work, Kipps, who holds the Evelyn and Edwin Tasch Chair in Cancer Research at UCSD, and colleagues, found breast cancer cells from patients with breast adenocarcinoma expressing high levels of ROR1 were more likely to have high rates of relapse and metastasis than those expressing low levels. They were also more likely to have EMT genes switched on.

Conversely, when they switched off the ROR1 gene in animals bred to have this form of breast cancer, it reversed EMT and stopped the cancer cells from spreading.

And when they targeted ROR1 with a monoclonal antibody, it stopped the growth and spread of highly metastatic tumors with cells that express ROR1.

Kipps and colleagues conclude their findings indicate “that ROR1 may regulate EMT and metastasis and that antibodies targeting ROR1 can inhibit cancer progression and metastasis”.

Monoclonal antibodies are a relatively new type of cancer treatment where lots of copies of one antibody are made by identical immune cells. The antibody is designed to target a specific protein on the surface of cancer cells.

For instance, in 2011, researchers in France reported how the monoclonal antibody denosumab can delay onset of bone metastases in prostate cancer patients by inhibiting RANKL, a protein involved in bone metabolism.

In a statement, first author Bing Cui, a post-doctoral fellow in Kipps’ lab, says you might think of ROR1 as an “oncogene”, a gene that promotes cancer.

“However, ROR1 also appears to allow transformed cells to invade other tissues and to promote tumor expansion in both the primary tumor site and in distant organs,” says Cui.

As it is only switched on cancer cells, the researchers believe ROR1 is an ideal target for a selective anti-cancer drug that would not attack healthy cells.

They cannot say how well the monoclonal antibody method would work in humans because they only tested in in cultured cells and in animals.

However, they are already developing a humanized form for clinical testing in patients with cancers that express ROR1.

Funds from the National Institutes of Health, the California Institute of Regenerative Medicine and the Blood Cancer Research Fund, UC San Diego Foundation helped pay for the study.

Written by Catharine Paddock PhD