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Cancer Summit 2007 Using Time-lapse Microscopy to Learn How Tumor Cells Migrate & Invade 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 Animal Clinical experiments studies & Trials drug development New Treatment 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 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 “Basic” biomedical research Initial discovery Recognition of relevance Early Animal Clinical experiments studies & Trials drug development New Treatment 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 Tissues are composed of orderly arrays of many individual cells 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 Epithelial cells use proteins to interact with each and with the “extracellular matrix” cell adhesion molecules “matrix” receptors 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 Tumor cells can be propagated & studied in the lab Incubator Flasks & growth medium Biosafety cabinet Cell culture microscope Time-lapse video-microscopy can be used to study tumor cell behavior Different tumor cell responses to different matrix proteins QuickTime™ and a None decompressor are needed to see this picture. protein A protein B protein C mixture of different matrix proteins Tumor cells use different matrix receptors to respond to different matrix proteins Receptor A matrix protein A (slow migration) matrix protein B (medium migration) “Receptor C”, which allows the most rapid migration, has extra accessory proteins Receptor B Receptor C matrix protein C (fast migration) Removing accessory proteins from the migrationpromoting matrix receptor attenuates tumor cell motility QuickTime™ and a Sorenson Video 3 decompressor are needed to see this picture. Migrating tumor cells must “let go” at the rear in order to keep moving forward Loss of “Receptor C” accessory proteins may impair the ability of tumor cells to “let go” during migration QuickTime™ and a Sorenson Video 3 decompressor are needed to see this picture. Tumor cells engineered to glow like fireflies can be used to follow disease in mouse models of cancer Acknowledgments Lab Members Collaborators Research Associates Afshin Varzavand Nicole Winterwood Jess Johnson Michael Henry, University of Iowa Postdoctoral Fellow Mary Herndon Leonie Ashman University of Newcastle, Australia Sponsors American Cancer Society Graduate Student Shannin Zevian Carver Foundation Department of Defense U.I. Biosciences Funding Program