The Center for Translational Cancer Research

Mechanisms of Motility and Metastasis

During cancer progression, cancer cells acquire the ability to leave their site of origin and migrate to other sites in the body, a process known as metastasis. In most cases, cancer is not a deadly disease unless this motility change occurs. Thus, a major focus of research in the CTCR is the study of the mechanisms by which stationary cells transform into migratory cells and the identification of drugs to prevent this process or treat cancers that have already metastasized. Several collaborative projects are underway that seek to address these processes with the aim of developing new methods to stop further cancer metastasis and shrink secondary tumors at sites such as in liver, bone, brain, or lung.

One project examines movement of cancer cells, including glioma and breast cancer cells, along nerve axon tracts and blood vessels. As an example, brain metastases from breast cancer are often lethal within weeks to months, and the research being conducted examines mechanisms of metastasis, including homing to brain and tumor cell invasion into tissue through blood vessels ("extravasation"), with the hope of finding new ways to stop this from occurring.

Another cooperative project studies the role of RhoC GTPase in metastasis of a breast, prostate and pancreatic cancer. RhoC is a homologue of the Ras oncogene and belongs to the Rho-subfamily of small GTPases. RhoC is the third member of this subfamily comprised of RhoA, RhoB, and RhoC, and is involved in reorganization of the actin cytoskeleton leading to cellular motility and invasion. Novel drugs targeting this pathway are under study with the hope that they would be useful for stopping tumor cells in their tracks.

Collaborations between material sciences and biological sciences have lead to a project aimed at developing a three-dimensional (3D) cell culture system to replicate the bone marrow microenvironment of cancer cells that have metastasized to the bone. The 3D system used in this project is a hydrogel, a biocompatible network that swells in the presence of water. Cancer cells can be introduced into this network where they proliferate to form "tumors". Using this 3D system, CTCR researchers have developed a new method of testing drugs to treat bone metastatic prostate cancer. Additionally, a novel 3D invasion/migration assay to better study the process of metastasis is being developed using this system.