decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft modeldecorin蛋白质核心影响全球基因表达谱三阴性的肿瘤微环境原位乳腺癌异种移植模型.pdf

Decorin Protein Core Affects the Global Gene Expression Profile of the Tumor Microenvironment in a Triple- Negative Orthotopic Breast Carcinoma Xenograft Model 1. 1. 2 3 1 Simone Buraschi , Thomas Neill , Rick T. Owens , Leonardo A. Iniguez , George Purkins , 1 1 4 1 1 Rajanikanth Vadigepalli , Barry Evans , Liliana Schaefer , Stephen C. Peiper , Zi-Xuan Wang , Renato V. Iozzo1* 1 Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 2 LifeCell Corporation, Branchburg, New Jersey, United States of America, 3 Roche NimbleGen, Inc., Research and Development, Madison, Wisconsin, United States of America, 4 Department of Pharmacology, Goethe University, Frankfurt, Germany Abstract Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that decorin protein c