January 18, 2007
In the early 1970s, Dr. Judah Folkman first proposed that after reaching a critical mass, tumor cells must induce nearby blood vessels to grow into the tumor and deliver the needed supply of nutrients to fuel their continued growth. Although largely ignored at the time, Folkman’s concept of tumor angiogenesis now is a cornerstone of cancer research and has led to the identification of numerous angiogenic proteins. Among them is the protein Semaphorin 4D, or Sema4D. Recent studies indicate that many human tumors overexpress this protein specifically to promote the growth of blood vessels. The process works like this: Sema4D first binds to its receptor on the surface of blood vessel lining endothelial cells. Thereafter, an enzyme cleaves Sema4D free from its receptor, allowing the protein to matriculate to nearby endothelial cells and induce them to branch into new blood vessels.
As published online on January 4 in the Journal of Biological Chemistry, NIDCR scientists have identified the enzyme that cleaves Sema4D free from its receptor, an important lead in further delineating and potentially blocking the process. The enzyme, called MT1-MMP, is tethered to the cell membrane, where it first helps to process Sema4D and then cleaves it loose. The scientists found that MT1-MMP was present in several head and neck tumor cells but, interestingly, was not expressed in normal epithelial cells lines.