Synthetic Molecule Targets Collagen, Cancer

A synthetic molecule known as collagen mimetic peptide (CMP) can home in on cancerous sites in the body (PNAS published online 2012 Aug 27). Affixed with a fluorescent tag, the peptide could offer new opportunities for detecting early-stage malignancies, says senior author S. Michael Yu, PhD, a faculty member in the materials science and engineering department at Johns Hopkins University in Baltimore, MD.

CMP doesn't bind to cancer cells, but rather to shreds of degraded collagen. As a scaffold in tissue, collagen ordinarily coils into a rope-like helical structure, much like the double helix of DNA. Those coils get stripped apart and remodeled as collagen degrades during normal processes such as bone growth and wound healing.

Growing tumors also make room for themselves by degrading collagen with proteolytic enzymes. This degradation exposes single-stranded collagen fibers to which CMP readily binds. “The binding makes a triple helix similar to what you see in natural collagen,” Yu says.

Because CMP molecules stick together, Yu and his collaborators separate the peptides by encasing them each in chemical “cages” that can be triggered to open under intense ultraviolet light. During their investigation, they “uncaged” the peptides this way and immediately injected them into mice bearing either prostate or pancreatic tumor xenografts. In vivo fluorescence imaging reveals CMPs accumulating both at the cancer sites and also where tissue modeling occurs routinely, such as knee joints.

In this fluorescent in vivo image, red indicates the highest intensity of collagen mimetic peptide binding, in prostate tumor xenografts in a mouse's shoulder areas.