1. Cancer Summit 2007 Using Time-lapse Microscopy to Learn How Tumor Cells Migrate & Invade

2. Covering the distance between discovery and treatment is a team effort No one research group can do it alone The significance of new discoveries is not always immediately obvious Initial discovery Recognition of relevance Early experiments Animal studies & drug development Clinical Trials New Treatment

3. Discoveries relevant to cancer treatment can come from unexpected places 1950s Discovery of Nerve Growth Factor Rita Levi-Montalcini 1960s Characterization of Epidermal Growth Factor (EGF) Stanley Cohen 1980s Identification of EGF Receptor 1998 Herceptin approved for treatment of metastatic breast cancer

4. Covering the distance between discovery and treatment is a team effort No one research group can do it alone The significance of new discoveries is not always immediately obvious Initial discovery Recognition of relevance Early experiments Animal studies & drug development Clinical Trials New Treatment “Basic” biomedical research

5. Metastasis is responsible for most cancer-related deaths but remains poorly understood Metastasis in non-Hodgkins lymphoma Figure 14.1 from “The Biology of Cancer,” Robert A. Weinberg, 2007, Garland Science

6. Tissues are composed of orderly arrays of many individual cells

7. Cells use proteins to accomplish necessary functions Information encoded by genes is used to produce individual proteins Proteins fold into many different shapes to fulfill different functions

8. Epithelial cells use proteins to interact with each and with the “extracellular matrix” cell adhesion molecules “matrix” receptors

9. Cancer progression involves changes in cell-cell and cell-matrix interactions Cell-cell interactions may be disrupted Cell-matrix interactions may be used for invasion and migration

10. Tumor cells can be propagated & studied in the lab Incubator Flasks & growth medium Cell culture microscope Biosafety cabinet

11. Time-lapse video-microscopy can be used to study tumor cell behavior

12. Different tumor cell responses to different matrix proteins mixture of different matrix proteins protein Aprotein Bprotein C

13. Tumor cells use different matrix receptors to respond to different matrix proteins matrix protein A (slow migration) matrix protein B (medium migration) matrix protein C (fast migration) “Receptor C”, which allows the most rapid migration, has extra accessory proteins Receptor A Receptor B Receptor C

14. Removing accessory proteins from the migration- promoting matrix receptor attenuates tumor cell motility

15. Migrating tumor cells must “let go” at the rear in order to keep moving forward

16. Loss of “Receptor C” accessory proteins may impair the ability of tumor cells to “let go” during migration

17. Tumor cells engineered to glow like fireflies can be used to follow disease in mouse models of cancer

18. Acknowledgments Lab Members Postdoctoral Fellow Mary Herndon Graduate Student Shannin Zevian Research Associates Afshin Varzavand Nicole Winterwood Jess Johnson Collaborators Michael Henry, University of Iowa Leonie Ashman University of Newcastle, Australia Sponsors American Cancer Society U.I. Biosciences Funding Program Carver Foundation Department of Defense