title: Identification of a stable molecular signature in mammary tumor endothelial cells that persists in vitro.
abstract: Long-term, in vitro propagation of tumor-specific endothelial cells (TEC) allows for functional studies and genome-wide expression profiling of clonally derived, well-characterized subpopulations. Using a genetically engineered mouse model of mammary adenocarcinoma, we have optimized an isolation procedure and defined growth conditions for long-term propagation of mammary TEC. The isolated TEC maintain their endothelial specification and phenotype in culture. Furthermore, gene expression profiling of multiple TEC subpopulations revealed striking, persistent overexpression of several candidate genes including Irx2 and Zfp503 (transcription factors), Alcam and Cd133 (cell surface markers), Ccl4 and neurotensin (Nts) (angiocrine factors), and Gpr182 and Cnr2 (G protein-coupled receptors). Taken together, we have developed an effective method for isolating and culture-expanding mammary TEC, and uncovered several new TEC-selective genes whose overexpression persists even after long-term in vitro culture. These results suggest that the tumor microenvironment may induce changes in vascular endothelium in vivo that are stably transmittable in vitro.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 3340C Medical Biomolecular Research Building, Chapel Hill, NC, 27599, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.forename: J Chuck
authors.initials: JC
authors.lastname: Harrell
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dudley
mesh_terms: D000818:Animals; D002469:Cell Separation; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D016678:Genome; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice