The role of Survivin in Glioma cell migration and proliferation

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1 The role of Survivin in Glioma cell migration and proliferation BY: MIGUEL MONTANA UNDER THE DIRECTION OF: DR. CHRISTINE MARSHALL-WALKER BIOLOGY 600/610

2 The life cycle of a healthy cell Healthy cells follow regulatory check points. A healthy cell follows a strict lifecycle. Every action like growth must first be signaled by the body. For example wound repair.

3 An introduction to cancer: cancerous cells Cancer cells are mutated forms of healthy cells. These mutations often allow the cancer to bypass regulatory checkpoints. These cells then begin to reproduce rapidly without being prompted to do so.

4 Survivin: an Inhibitor of Apoptosis Apoptosis is the term given to a cell s natural death. Inhibitors of Apoptosis allow aging or mutated cells to bypass the regulatory checkpoint that would normally force them to die. Survivin is naturally found in most vertebrates.

5 Survivin: an Inhibitor of Apoptosis However, in mammals, survivin is only found in fetuses and embryos. Survivin is useful for growth in utero because it allows rapid development. It is especially important for the development of brain cells. When cells become cancerous, they also produce survivin, which allows them to reproduce extremely quickly.

6 Survivin: a protein for cell movement Cells contain a scaffolding called a cytoskeleton which can change shape as needed. Survivin has been linked to be a protein that may helps lay and maintain some cancer cells framework. As a result it was hypothesized that survivin might be important for movement and cell s vitality.

7 Glioma cells: Glioblastoma Multiforme The cells observed for this study were rat C6 Glioma cells and U87 Glioma cells. Gioma cells lead to one of the most common cancers: Gioblastoma Multiforme (GBM). GBM also has one of the highest mortality rates for any cancer.

8 Glioma cells: Glioblastoma Multiforme Why is GBM so destructive? The glioma cells are highly migratory and form inoperable tumors. Chemotherapy is less effective at treating brain cancers because of the blood-brain barrier. Glioma cells are highly resilient and prolific, so even with successful chemotherapy, surgery, and radiation GBM often returns.

9 Survivin s potential for therapeutic intervention. Most GBM patients are adults and the protein is not found in adult humans. It is important for cytoskeletal formation in other cancer types and could be important in movement as a result. It is important for cancer proliferation and has been proven to be important in other cancers reproduction. These three characteristics render it ideal for medical purposes. It could be used to guide medicine or it could be genetically silenced without hurting healthy cells.

10 Experimental approach Proliferation Assays Migration Assays Using a method known as RNAi (RNA interference), the gene coding for survivin was heavily silenced in treated cells. A set number of treated and untreated cells were allowed to migrate through a filter that resembles brain tissue. Several experimental groups were created and allowed to grow for different time intervals. The difference in the number of cells migrating was quantified. The difference in the final cell populations were compared.

11 Proliferation Assays Human Glioma cells Rat Glioma cells 120 Percent cells alive compared to control Percent of cells alive compared to control day control 2 day control 1 day 2 day 1 day control 2 day control 1 day 2d (5,000) (2,500) experimental experimental (5,000) (2,500) experimental experimental (5,000) (2,500) (5,000) (2,500)

12 Migration Assay Human Glioma Cells Rat Glioma cells percent migration compared to control Day Control 1 Day Experimental 2 Day Experimental 1 Day Control 2 Day Control 1 Day Experimental 2 Day Experimental

13 Summary Survivin is required for the proliferation and survival of rat and human Glioma cells. Survivin also may be important for the migration of Glioma cells. These results underscore the importance of Survivin as a potential therapeutic reagent for treating brain cancer.

14 Acknowledgements Dr.Peter Canoll (Columbia University, New York) Dr.Christine Marshall-Walker Ms. Melanie Poulin