New Notre Dame study provides insights into the molecular basis of tumor cell behavior

A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.

The study elucidates mechanisms involved in the release of microvesicles –small membrane enclosed sacs– from tumor cells that facilitate creation of paths of least resistance allowing tumor cells to migrate. The research offers new insights into how tumor cells invade their surrounding environment and may eventually lead to improved methods for measuring the progression of cancers.

The research paper, which appears this week in an early online edition of the journal Current Biology, identifies a unique population of microvesicles that are enriched in proteases- mediators of tissue degradation. The release of these microvesicles provides a mechanism of tissue breakdown and remodeling at distant sites and is distinct from the better-characterized mechanisms involved in tissue degradation adjacent to the leading edge of tumor cells, D'Souza-Schorey notes.

The new study shows that microvesicle shedding requires localized contraction of the cell's cytoskeleton at sites of microvesicle release and identifies some key regulators involved in the process. One of these critical determinants is the protein ARF6. Understanding the role of the ARF6 protein in cancer progression has been a long standing interest of the D'Souza-Schorey laboratory. Earlier studies from the laboratory using cell and animal tumor models had documented a role of ARF6 in tumor cell invasion.