Collagen-Seeking Synthetic Protein can Spot Tumors
One of the hallmarks of cancer is that tumors alter the tissues that surround malignant cells. A team of investigators from Johns Hopkins has taken advantage of this hallmark to develop a new approach to identifying cancer that hones in on collagen that gets degraded as a tumor grows. The technique could lead to a new type of diagnostic imaging technology and may someday serve as a way to move medications to parts of the body where signs of disease have been found.
In a study published in the Proceedings of the National Academy of Sciences, researchers led by S. Michael Yu and Martin Pomper, report on their success in using a synthetic protein in mouse models to locate prostate and pancreatic cancers, as well as to detect abnormal bone growth activity associated with Marfan syndrome. Dr. Pomper is co-principal investigator of the Johns Hopkins Center of Cancer Nanotechnology Excellence.
The synthetic protein developed by the Hopkins team does not zero in directly on the diseased cells. Instead, it binds to nearby collagen that has been degraded by various health disorders. 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 diseased cells such as cancer can send out enzymes that break down and reform collagen at an accelerated pace. It is this excessive remodeling, caused by disease, that the new synthetic protein can detect, the researchers said.
“A major unmet medical need is for a better non-invasive characterization of disrupted collagen, which occurs in a wide variety of disorders,” Pomper said. “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 proteins used in the study are called collagen mimetic peptides or CMPs. These tiny bits of protein are attracted and physically bind to degraded strands of collagen, particularly those damaged by disease. Fluorescent tags are placed on each CMP so that it will show up 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, similar to DNA, in a way that would cause them to ignore the disease-linked collagen targeted by the researchers. To remedy this, the investigators synthesized CMPs that possess 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.
The researchers tested these 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.
This work, which is detailed in a paper titled, “Targeting collagen strands by photo-triggered triple-helix hybridization,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.