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

Yang Liu, Eleanor B. Carson-Walter, Anna Cooper, Bethany N. Winans, Mahlon Johnson, Kevin A. Walter

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalJournal of Neuro-Oncology
Volume99
Issue number1
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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Brain Neoplasms
Blood Vessels
Microvessels
Gene Expression
Neoplasms
Genes
Polymerase Chain Reaction
Brain
Glioblastoma
Glioma
Neuroglia
In Situ Hybridization
Extracellular Matrix
Immunohistochemistry
Neoplasm Metastasis
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Vascular gene expression patterns are conserved in primary and metastatic brain tumors. / Liu, Yang; Carson-Walter, Eleanor B.; Cooper, Anna; Winans, Bethany N.; Johnson, Mahlon; Walter, Kevin A.

In: Journal of Neuro-Oncology, Vol. 99, No. 1, 01.08.2010, p. 13-24.

Research output: Contribution to journalArticle

Liu, Yang ; Carson-Walter, Eleanor B. ; Cooper, Anna ; Winans, Bethany N. ; Johnson, Mahlon ; Walter, Kevin A. / Vascular gene expression patterns are conserved in primary and metastatic brain tumors. In: Journal of Neuro-Oncology. 2010 ; Vol. 99, No. 1. pp. 13-24.
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