| | Category | BMEN | L08 | High-dimensional Single-cell Cytometry Analysis of Cancer |
| | Stemness |
| | Abstract | While cancer starts as a single cell, termed cancer stem cell (CSC), the |
| | progeny CSCs are not created equal, but exhibit a spectrum of |
| | phenotypes of varying renewal capacity, metastatic potential, and drug |
| | resistance (1). Understanding this cell-to-cell difference (i.e. |
| | heterogeneity) of CSCs holds the key to both scientific and translational |
| | cancer research and presents us the opportunity to target and |
| | eliminate cancer at its “stem”. Unfortunately, we do not currently have |
| | the tools necessary to dissect CSC heterogeneity due to multiple |
| | limitations (2). First, CSCs are extremely rare, making their isolation |
| | parallel with finding a needle in a haystack; Second, not all biomarkers |
| | on CSC subpopulations are known; Third, there is currently no single- |
| | cell proteomic and signaling analyses of CSCs available; Finally, CSCs |
| | are not static, but evolve with interacting symbiotic cells. As a result, our |
| | current view of CSCs is “pixelated” and “isolated”, keeping us far away |
| | from the complete understanding of CSCs. |
| | |
| | To overcome some of the limitations mentioned above, we harvested |
| | the power of a recent technological advancement in single-cell |
| | detection, namely cytometry by time-of-flight (CyTOF) (3). The |
| | University of Michigan is among the first to bring this technology on |
| | campus. Using CyTOF, I have successfully collected and then profiled |
| | the high-dimensional cytometry data obtained from an antibody panel |
| | that allows for simultaneous measurement of 27 markers on a single |
| | cell at a rate of 1000 cells per second. For the first time, we were able |
| | to directly detect breast cancer CSCs. With further antibody panel |
| | expansion and data mining, this study will provide the first |
| | comprehensive and high-resolution map of the CSC subpopulations at |
| | the proteomic and signaling levels. These results will unlock the |
| | answers to central questions regarding cancer stemness, which will |
| | change the paradigm of current practices in several aspects of cancer |
| | medicine, including early detection, monitoring, therapeutics, and |
| | ultimately lead to the development of preventative strategies to |
| | suppress or even reverse the initiation of cancer. |
| | Bibliography | Visvader JE. Cells of origin in cancer. Nature. 2011;469(7330):314-22. |
| | Epub 2011/01/21. doi: 10.1038/nature09781. PubMed PMID: |
| | 21248838.Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, La |
| | Noce M, et al. Cancer stem cells in solid tumors: an overview and new |
| | approaches for their isolation and characterization. FASEB journal : |
| | official publication of the Federation of American Societies for |
| | Experimental Biology. 2013;27(1):13-24. Epub 2012/10/02. doi: |
| | 10.1096/fj.12-218222. PubMed PMID: 23024375. |