Scientists at Stanford University say they have developed a protein therapy that disrupts the process that causes cancer cells to metastasize. The researchers focus on preventing two proteins—Axl and Gas6—from interacting to initiate the spread of cancer.
Axl proteins stand like bristles on the surface of cancer cells, poised to receive biochemical signals from Gas6 proteins. When two Gas6 proteins link with two Axls, the signals that are generated enable cancer cells to leave the original tumor site, migrate to other parts of the body, and form new cancer nodules.
To stop this process, described in an article (“An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis”) in Nature Chemical Biology, Jennifer Cochran, Ph.D., an associate professor of bioengineering, and colleagues used protein engineering to create a harmless version of Axl that acts like a decoy. This decoy Axl latches onto Gas6 proteins in the bloodstream and prevents them from linking with and activating the Axls present on cancer cells.
The Stanford team gave intravenous treatments of this bioengineered decoy protein to mice with aggressive breast and ovarian cancers. Mice in the breast cancer treatment group had 78% fewer metastatic nodules than untreated mice. Mice with ovarian cancer had a 90% reduction in metastatic nodules when treated with the engineered decoy protein.
“The engineered decoy receptor bound Gas6 with femtomolar affinity, an 80-fold improvement compared to binding of the wild-type Axl receptor, allowing effective sequestration of Gas6 and specific abrogation of Axl signaling,” wrote the investigators. “Moreover, increased Gas6 binding affinity was critical and correlative with the ability of decoy receptors to potently inhibit metastasis and disease progression in vivo.”
“This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” said Amato Giaccia, Ph.D., who heads the radiation biology program in Stanford's Cancer Center. “It could open up a new approach to cancer treatment.”