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Identification of a stable molecular signature in mammary tumor endothelial cells that persists in vitro

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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.

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Acknowledgments

ACD is supported by grants from the National Institute of Health (R00-CA140708) and the University Cancer Research Fund at UNC Chapel Hill. LX is a scholar in the HHMI-funded translational medicine program at UNC Chapel Hill. We would like to thank Mimi Kim and Clayton Davis for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 3340C Medical Biomolecular Research Building, Chapel Hill, NC, 27599, USA

    Lin Xiao & Andrew C. Dudley

  2. Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA

    J. Chuck Harrell, Charles M. Perou & Andrew C. Dudley

  3. Departments of Genetics and Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Charles M. Perou

  4. McAllister Heart Institute, Chapel Hill, NC, USA

    Andrew C. Dudley

Authors
  1. Lin Xiao
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  2. J. Chuck Harrell
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  3. Charles M. Perou
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  4. Andrew C. Dudley
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Correspondence to Andrew C. Dudley.

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Xiao, L., Harrell, J.C., Perou, C.M. et al. Identification of a stable molecular signature in mammary tumor endothelial cells that persists in vitro. Angiogenesis 17, 511–518 (2014). https://doi.org/10.1007/s10456-013-9409-y

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  • DOI: https://doi.org/10.1007/s10456-013-9409-y

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