Cancer Cell Migration, Invasion and Metastasis

Cancer is a major cause of death in the United States and the spread of cancer cells from a primary tumor to other organs, i.e. metastasis, is the key feature that leads to high mortality. For example, women with localized breast tumors have a 98% 5-year survival rate. However, metastasis of local breast tumors to other organs leads to a very low 23% survival rate. Metastasis involves the detachment of epithelial cells from the primary tumor, cell migration into the surrounding tissue, cell invasion into blood/lymphatic vessels and colonization of distal organs. One biological mechanism responsible for metastasis is known as epithelial to mesenchymal transition (EMT). EMT is a form of cell-plasticity (i.e. stem cell like behavior) where non-motile epithelial cells get converted into a highly migratory/invasive mesenchymal cell. EMT is normal assessed by measuring the activity of certain genes that are modulated during the transition. Unfortunately, many of these gene markers are non-specific and do not undergo consistent changes during metastasis. Furthermore, these markers do not provide a quantitative way to determine the degree of EMT and/or the metastatic potential in a given patient.

Recently, our laboratory has demonstrated that cancer cells undergo dramatic biomechanical and structural changes during EMT (see Figure 1). Not only are these biomechanical changes are highly-specific, since characterizing cell/tissue mechanics is a clinical viable diagnostic technique, these changes in cell mechanics represents a novel way to quantitatively assess the degree of EMT. However, it is not well understood how changes in cell mechanics facilitate or alter the cell migration and invasion processes required for metastasis. We have therefore started to develop sophisticated multi-scale computational models to investigate how changes in different cell biomechanical properties influence cancer cell migration and metastasis (see Figure 2). These models can simulate both the detachment of cancer cells from the primary tumor and their migration/invasion into surrounding tissues. For the summer projects, students will first be exposed to the computational tools used to create models of cancer cell migration and invasion (i.e. finite element modeling). The student team will then be ask to model a very specific and important step in metastasis where cancer cells that have detached from the primary tumor must squeeze through pores in the extracellular matrix and invade through a thin layer of endothelial cells to enter the blood stream. Two PhD students from Dr. Ghadiali’s lab will be available to help students set-up initial models and analyze model results. These students will also describe how they are using computational techniques to advance their PhD research programs.

Sponsored in part by NSF grant 1134201