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2013 Scientific Report

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VARI |

VARI | 2013 Genetics and phenotypes of cancer cell subsets Not all cancer cells within a tumor are equivalent. The more advanced and aggressive cells are proposed to be primarily responsible for the migration and spread of cancer (metastasis) and for resistance to chemotherapeutics. An improved understanding of the molecular characteristics and origins of these subtypes could help to specifically eliminate them. We have approached this problem by comparing the molecular characteristics of pancreatic cancer cells that appear mesenchymal (migratory) to those that appear epithelial (stationary), and we have identified several consistent differences. One difference is the overexpression of the cell surface protein MRC2 in mesenchymal-like cancer cells. MRC2 has a primary function of helping cells to recognize and degrade the extracellular matrix that surrounds them. We now are investigating whether MRC2 is specifically up-regulated in pancreatic cancer cells that are transitioning to a mesenchymal state. Another difference is in the particular genetic alterations characteristic of mesenchymal-like cancer cells. We are determining which of those alterations are most prevalent in primary tumors and which contribute to the behavioral changes of the cancer cells. We plan to build on these studies to improve methods for assessing and treating pancreatic cancer. New tools for studying specific carbohydrate structures We are developing novel methods for studying carbohydrates in human tissue samples. In particular, we are developing new molecular reagents that bind specific carbohydrate structures and so can be used to detect and measure them. Such reagents are unavailable for many carbohydrates that may be overexpressed in cancer tissue. We are using new bioinformatics methods developed by us and collaborators that allow us to search publicly available information on naturally occurring proteins that have carbohydrate-binding properties. Once we identify potentially useful reagents, we test them with our antibody and protein array technologies, optimize them, and then evaluate them in the analysis of carbohydrates in clinical specimens. These tools have value for our pancreatic cancer studies and the potential for broader scientific use in various glycobiology studies. Recent Publications Haab, B. 2012. Using lectins in biomarker research: addressing the limitations of sensitivity and availability. Proteomics Clinical Applications 6(7-8): 346–350. Partyka, Katie, Kevin A. Maupin, Randall E. Brand, and Brian B. Haab. 2012. Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation. Proteomics 12(13): 2212–2220. Partyka, Katie, Mitchell McDonald, Kevin A. Maupin, Randall Brand, Richard Kwon, Diane M. Simeone, Peter Allen, and Brian B. Haab. 2012. Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification. Journal of Proteome Research 11(5): 2904–2911. Maupin, Kevin A., Daniel Liden, and Brian B. Haab. 2011. The fine specificity of mannose-binding and galactose-binding lectins revealed using outlier motif analysis of glycan array data. Glycobiology 22(1): 160–169. Yue, Tingting, Kevin A. Maupin, Brian Fallon, Lin Li, Katie Partyka, Michelle A. Anderson, Dean E. Brenner, Karen Kaul, Herbert Zeh, A. James Moser, et al. 2011. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers. PLoS One 6(12): e29180. 27

Galen H. Hostetter, M.D. Laboratory of Analytical Pathology Dr. Hostetter received his M.D. degree from the University of Pennsylvania in 1993, and he is board-certified in pathology. He has completed medical and cancer genetics fellowships at the National Institutes of Health. His primary research interest has been applications of genomic assays and validation in clinical samples using tissue microarrays. He was staff pathologist at the Translational Genomics Research Institute (TGen) from 2003 to 2011. Dr. Hostetter joined VARI in 2011 as an Assistant Professor and head of the Laboratory of Analytical Pathology within the Program for Biospecimen Science (PBS). Staff Bree Berghuis, B.S., HTL(ASCP), QIHC Eric Hudson, B.S. Lisa Turner, B.S., ST(ASCP), QIHC Students Eric Edewaard Peter Varlan 28

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