Tadpole research may help fight tumours

There's something magical about tadpoles. The mere mention of this little creature sparks happy memories of children screaming with delight as they splash in a shallow stream trying to capture some of the tiny swimmers in a cup. The real magic happens as the children witness the metamorphosis from tadpole to frog.

Within the mystery of this transformation is a biological series of changes that among other things, allows one appendage to be shed while four others sprout from the tadpole's body. Before a tadpole becomes a frog, it must lose its tail. A time-lapse video of this process would actually reveal that the tadpole tail doesn't simply fall off but rather grows shorter in a process called tail resorption.

Scientists who study this process on a molecular level have known that a protein called FAP (fibroblast activation protein) is involved in tail resorption. However, FAP may have a much more perverse role in humans.

"We know that FAP helps control the breakdown of the extracellular matrix that allows tadpole tail resorption, and we believe that the same type of activity has to happen for tumor growth," said Jonathan D. Cheng, M.D., a medical oncologist and researcher at Fox Chase Cancer Center. "We are currently investigating how the two may be related biologically.

"Animal studies have shown that producing lots of FAP in the tumor's microenvironment makes the cancer grow faster. We are now learning more about how FAP does that."

In a study presented today at the 95th Annual Meeting of the American Association for Cancer Research in Orlando, Fla., Cheng and his colleagues demonstrate that the enzymatic activity of FAP is responsible for the accelerated tumor growth in mice. Cheng's research also examines the ability of an antibody molecule to stop the enzymatic activity of FAP.

"We know that FAP is present in about 90 percent of human solid malignancies, so that makes this protein a target well worth pursuing," Cheng said. "Antibodies have an inherent advantage in that they can specifically target FAP and not other proteins. Although the antibody we have studied so far has had only modest results to date, we are making some modifications to our existing antibodies to improve the molecule's ability to block FAP's action. Much more research lies ahead."

Fox Chase Cancer Center, one of the nation's first comprehensive cancer centers designated by the National Cancer Institute in 1974, conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu.