Microarray gene expression analysis of murine tumor heterogeneity defined by dynamic contrast-enhanced MRI

Nick G. Costouros, Dominique Lorang, Yantian Zhang, Marshall S. Miller, Felix E. Diehn, Stephen M. Hewitt, Michael V. Knopp, King C.P. Li, Peter L. Choyke, H. Richard Alexander, Steven K. Libutti

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Current methods of studying angiogenesis are limited In their ability to serially evaluate In vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of Increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalMolecular Imaging
Volume1
Issue number3
DOIs
StatePublished - Jul 1 2002

Keywords

  • Gadolinium
  • Gene expression
  • Laser capture microdissection
  • Magnetic resonance imaging
  • Microarray

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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  • Cite this

    Costouros, N. G., Lorang, D., Zhang, Y., Miller, M. S., Diehn, F. E., Hewitt, S. M., Knopp, M. V., Li, K. C. P., Choyke, P. L., Alexander, H. R., & Libutti, S. K. (2002). Microarray gene expression analysis of murine tumor heterogeneity defined by dynamic contrast-enhanced MRI. Molecular Imaging, 1(3), 301-308. https://doi.org/10.1162/153535002760235481