Protein sticks to damaged collagen near cancer

JOHNS HOPKINS (US) — A new synthetic protein can detect cancer and other diseases in the body by finding and latching onto damaged collagen nearby, scientists say.

The protein’s developers hope it will lead to a new type of diagnostic imaging technology. It someday may also be used to move medication to target areas where signs of disease have been found.

In a study published in the Proceedings of the National Academy of Sciences, the researchers reported using the synthetic protein to locate prostate and pancreatic cancer tumors in mice. They also were able to detect abnormal bone growth from Marfan syndrome.

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Rather than zeroing in directly on diseased cells, the protein binds to nearby collagen the disease has degraded. Collagen, the body’s most abundant protein, provides structure and creates a sturdy framework upon which cells build nerves, bone, and skin.

Some buildup and degradation of collagen is normal, but disease cells such as cancer can send out enzymes that break down collagen at an accelerated pace. It is this excessive damage that the new synthetic protein can detect, Johns Hopkins researchers say.

“These disease cells are like burglars who break into a house and do lots of damage but who are not there when the police arrive,” explains principal investigator Michael S. Yu, associate professor of materials science and engineering in the university’s Whiting School of Engineering. “Instead of looking for the burglars, our synthetic protein is reacting to evidence left at the scene of the crime.”

A key collaborator was Martin Pomper, a School of Medicine professor and co-principal investigator of the Johns Hopkins Center of Cancer Nanotechnology Excellence. Pomper and Yu joined forces through the Johns Hopkins Institute for NanoBioTechnology.

“A major unmet medical need is for a better non-invasive characterization of disrupted collagen, which occurs in a wide variety of disorders,” says Pomper, a radiologist. “Michael has found what could be a very elegant and practical solution, which we are converting into a suite of imaging and potential agents for diagnosis and treatment.”

The synthetic protein—a collagen mimetic peptide, or CMP—is attracted to and physically binds with degraded strands of collagen, particularly those damaged by disease. Fluorescent tags on the CMP glow when doctors scan tissue with fluorescent imaging equipment. The glowing areas indicate the location of damaged collagen that is likely to be associated with disease.

In developing the technique, the researchers faced a challenge because CMPs tend to bind with one another and form their own structures in a way that would cause them to ignore the disease-linked collagen targeted by the researchers.

To remedy this, the study’s lead author, Yang Li, synthesized CMPs with a chemical “cage” to keep the proteins from binding with one another. Just prior to entering the bloodstream to search for damaged collagen, a powerful ultraviolet light is used to “unlock” the cage and allow the CMPs to initiate their disease-tracking mission. Li is a doctoral student at Johns Hopkins. Yu is his adviser.

Yu’s team tested Li’s fluorescently tagged and caged peptides by injecting them into lab mice that possessed both prostate and pancreatic human cancer cells. Through a series of fluorescent images taken over four days, researchers tracked single strands of the synthetic protein spreading throughout the tumor sites via blood vessels and binding to collagen that had been damaged by cancer.

Similar in vivo tests showed that the CMP can target bones and cartilage with excess degraded collagen. Therefore, the new protein could be used for diagnosis and treatment related to bone and cartilage damage.

Although the process is not well understood, the breakdown and rebuilding of collagen is thought to play a role in the excessive bone growth found in patients with Marfan syndrome. Yu’s team tested their CMPs on a mouse model for this disease and saw increased CMP binding in the ribs and spines of the Marfan mice, as compared to the control mice.

The National Science Foundation, the National Institutes of Health, and the Department of Defense funded the work. The synthetic protein process used in this research is protected by patents obtained through the Johns Hopkins Technology Transfer Office.

Source: Johns Hopkins University