A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating metastasis. This finding was reported in Cancer Research (2013; doi:10.1158/0008-5472.CAN-12-3832).
Metastasis is responsible for 90% of cancer-related deaths. More than 575,000 Americans die of cancer each year, making it the second leading cause of death in the United States after cardiovascular disease.
Thomas Kipps, MD, PhD, of the University of California San Diego led a research team that discovered an association between the protein, known as receptor tyrosine kinase-like orphan receptor (ROR1), and the epithelia-mesenchymal transition (EMT). That is a process that occurs during embryogenesis when cells migrate and then grow into new organs during early development.
Last year, Kipps and colleagues reported for the first time that ROR1 is expressed during embryogenesis and by many different types of cancers, but not by normal postpartum tissues. They also discovered that silencing the protein impaired the growth and survival of human breast cancer cells.
The current work of these scientists found that high-level expression of ROR1 in breast cancer cells correlates to higher rates of relapse and metastasis in patients with breast adenocarcinoma, a type of cancer that originates in glandular tissue. Conversely, silencing expression of ROR1 reverses EMT and inhibits the metastatic spread of breast cancer cells in animal models. Moreover, the researchers found that treatment with a monoclonal antibody targeting ROR1 also could inhibit the growth and spread of highly metastatic tumors that express ROR1.
“We might think of ROR1 as an oncogene,” said study co-author Bing Cui, PhD, a postdoctoral fellow in Kipps’ laboratory. “This means ROR1 has some tumor initiation functions. 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.”
Because ROR1 is expressed only in cancer cells, Kipps’ team says it presents a singular, selective target for anticancer therapies that would leave normal cells unaffected. How the monoclonal antibody approach, tested thus far only in culture and animal models, impacts primary tumors is not yet clear, said Cui, but it does offer promise for inhibiting the spread of cancer. The researchers are developing a humanized monoclonal antibody for potential clinical studies in patients with cancers that express ROR1.