Developmental Protein Plays Role in Spread of Cancer
A protein used by embryo cells during early development, and recently found in many different types of cancer, may serve as a switch regulating metastasis, according to researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center. The findings were published in the June 15, 2013, issue of Cancer Research.
Led by principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research at UC San Diego, researchers discovered an association between the protein, called Receptor-tyrosine-kinase-like Orphan Receptor 1 or ROR1, and the epithelial-mesenchymal transition, a process that occurs during embryogenesis when cells migrate and then grow into new organs during early development.
In research published in 2012, Dr. 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.
Silencing ROR1 Expression
In their latest work, the 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. Conversely, silencing expression of ROR1 reverses epithelial-mesenchymal transition 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 coauthor Bing Cui, PhD, a postdoctoral fellow in Dr. Kipps’ lab. “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, the researchers say it presents a singular, selective target for anticancer therapies that would leave normal cells unaffected. It’s not yet clear how the monoclonal antibody approach, tested thus far only in culture and animal models, impacts primary tumors, said Dr. 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.
Funding for this research came, in part, from the National Institutes of Health (grant PO1-CA081534), the California Institute of Regenerative Medicine, and the Blood Cancer Research Fund, UC San Diego Foundation.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
