This finding, published in the current issue of the journal Genes and Development, marks the first report of a protein-cleaving enzyme, or protease, on the cell surface that can efficiently trigger the formation of tumor cells. The authors also note that matriptase is the first known cell-surface protease that can act as an oncogene, an umbrella term for mutated genes and their proteins that prompt cells to divide too rapidly, a hallmark of tumor cells.
"What makes matriptase potentially such a good molecular target to treat cancer is its accessibility," said NIDCR scientist Dr. Thomas Bugge, the senior author on the paper. "We don't have to trick the tumor cell to internalize a drug, then hope it reaches its destination in an appropriate concentration and duration. In this case, the bull's eye is right on the cell surface."
Bugge said the exact function of matriptase in healthy human cells remains a bit of a mystery. Previous studies show that cells comprising the outer lining, or epithelium, of nearly all human organs express the protease. They also suggest that matriptase might play a role in activating other membrane-bound proteins on the cell surface that are involved in signaling basic cellular activities, such as growth and motility.
Since its discovery nearly 13 years ago, scientists also have suspected that matriptase might have a dark side. It is overly abundant in a variety of epithelial-derived tumors, including breast, prostate, ovarian, colon, and oral carcinomas. Then, in 2002, scientists reported women with breast and ovarian cancer have poor prognoses if their tumors contain high levels of matriptase. In fact, just two months ago, researchers reported for the first time that increased
Contact: Bob Kuska
NIH/National Institute of Dental and Craniofacial Research