Live-Cell Surface Proteomic Characterization of Atypical Teratoid Rhabdoid Tumors Using High Throughout Multi-Color Flow
Olivier Ayrault, PhD, Institut Curie
Rajeev Vibhakar, MD/PhD, University of Colorado Denver
Atypical teratoid rhabdoid tumor (AT/RT) is a rare and fast-growing childhood tumor of the brain and spinal cord. While recent advances in DNA and RNA sequencing have given deep insights into the biology of cancer, about 90% of AT/RTs harbor a single deletion which leads to uncontrolled tumor growth. The lack of targetable genetic abnormalities in AT/RT makes it a tough target for therapy and hence radical new approaches are required to develop treatment. Cell surface markers are proteins expressed on the surface of cells that often conveniently serve as markers of specific cell types. In many cases the gene expression profile alone does not represent the presence of the gene product on the surface and also the presence of any post-translational modifications such as the addition of sugars which are essential for the interaction of surface proteins with the tumor microenvironment. Furthermore, the surface proteins are responsible for the ability of cancer cells to avoid detection and elimination by the body’s immune system. The ability to escape from surveillance by the immune system is regarded as one of the essential hallmarks of cancer cells. Here we propose a comprehensive unbiased large-scale surface receptor profiling using high throughput multicolor flow cytometry on surgically resected AT/RT patient samples (12 available), primary AT/RT cell lines (8 available) and patient derived xenograft models (5 available). Flow cytometry not only enables the identification of surface markers on live cells but also for prospective enrichment of cells and can be utilized to study specific cell-surface interactions in intact cells.