Journal of Neuro-Oncology

, Volume 99, Issue 1, pp 13–24 | Cite as

Vascular gene expression patterns are conserved in primary and metastatic brain tumors

  • Yang Liu
  • Eleanor B. Carson-Walter
  • Anna Cooper
  • Bethany N. Winans
  • Mahlon D. Johnson
  • Kevin A. Walter
Laboratory Investigation - Human/Animal Tissue


Malignant primary glial and secondary metastatic brain tumors represent distinct pathological entities. Nevertheless, both tumor types induce profound angiogenic responses in the host brain microvasculature that promote tumor growth. We hypothesized that primary and metastatic tumors induce similar microvascular changes that could function as conserved angiogenesis based therapeutic targets. We previously isolated glioma endothelial marker genes (GEMs) that were selectively upregulated in the microvasculature of proliferating glioblastomas. We sought to determine whether these genes were similarly induced in the microvasculature of metastatic brain tumors. RT-PCR and quantitative RT-PCR were used to screen expression levels of 20 candidate GEMs in primary and metastatic clinical brain tumor specimens. Differentially regulated GEMs were further evaluated by immunohistochemistry or in situ hybridization to localize gene expression using clinical tissue microarrays. Thirteen GEMs were upregulated to a similar degree in both primary and metastatic brain tumors. Most of these genes localize to the cell surface (CXCR7, PV1) or extracellular matrix (COL1A1, COL3A1, COL4A1, COL6A2, MMP14, PXDN) and were selectively expressed by the microvasculature. The shared expression profile between primary and metastatic brain tumors suggests that the molecular pathways driving the angiogenic response are conserved, despite differences in the tumor cells themselves. Anti-angiogenic therapies currently in development for primary brain tumors may prove beneficial for brain metastases and vice versa.


Glioblastoma Metastatic brain tumor Angiogenesis Endothelial genes Vascular genes 



We thank Dr. Sumana Datta of Texas A&M University for advice regarding HSPG2 immunohistochemical staining. This work was supported by the National Institutes of Health (NINDS K08 NS046461 to K.A.W.), the American Brain Tumor Association (to K.A.W.), the Childhood Brain Tumor Foundation (to K.A.W.) and the Ronald Bittner Brain Tumor Research Fund (to K.A.W.).

Supplementary material

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Supplementary material 1 (PDF 24 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Yang Liu
    • 1
  • Eleanor B. Carson-Walter
    • 1
  • Anna Cooper
    • 1
  • Bethany N. Winans
    • 1
  • Mahlon D. Johnson
    • 2
  • Kevin A. Walter
    • 1
    • 3
  1. 1.Department of NeurosurgeryUniversity of RochesterRochesterUSA
  2. 2.Department of NeuropathologyUniversity of RochesterRochesterUSA
  3. 3.James P. Wilmot Cancer CenterUniversity of RochesterRochesterUSA

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