How Cancers Metastasize
September 28, 2006, ANN ARBOR, Mich--- A new finding from the laboratory of Stephen Weiss at the University of Michigan provides important insights into cancer cells’ most deadly characteristic -- their ability to invade tissues and metastasize throughout the body. When cancers are discovered and treated before they spread, the likelihood of cure is much greater.
“We asked how cancer cells cut their way through tissues,” said Weiss, Life Sciences Institute Research Professor and Division Chief, Molecular Medicine & Genetics in the U-M Medical School. “They use what we call proteases, a type of molecular scissors. However, there are so many different types of these scissors encoded by the human genome, we wanted to focus our attention on finding the subset used by cancers.”
In all forms of cancer, a hallmark of malignancy is the tumor’s ability to penetrate the
basement membrane, a specialized form of connective tissue that lines the internal and external surfaces of the body including blood vessels, nerves, muscle and fat. The tumor cells appear to use a set of three enzymes to cut their way through the basement membrane, thus allowing cancer cells access to blood vessels which act as conduits for the spread of malignant cells to distant sites in the body.
Of the more than 500 enzymes that could be used by cells as molecular scissors, the Weiss team found that three proteases, termed MT1-MMP, MT2-MMP and MT3-MMP, are the most likely candidates that regulate cancer cell invasion.
“These closely related proteases allow cancer cells to start eating through basement membranes and the surrounding tissues. This is the first critical step in the malignant process and allows the rapid spread of cancer cells through the body.”
By identifying this set of proteases, the studies by Weiss and his colleagues have provided the first proof that a small set of gene genes and proteins may underlie the cancer cell metastatic process. While their work is still at an early stage, Weiss and co-workers are attempting to develop new inhibitors of these proteases to begin testing their importance in animal models of human cancer.
The paper, A cancer cell metalloprotease triad regulates the basement membrane transmigration program by Kevin Hotary, Xiao-Yan Li, Edward Allen, Susan L. Stevens and Stephen J. Weiss appeared as an advanced online publication in the journal Genes & Development and in print on October 1, 2006.
