Vascular gene expression patterns are conserved in primary and metastatic brain tumors |
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Authors: | Yang Liu Eleanor B Carson-Walter Anna Cooper Bethany N Winans Mahlon D Johnson Kevin A Walter |
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Institution: | (1) Department of Neurosurgery, University of Rochester, 601 Elmwood Avenue, Box 670, Rochester, NY 14642, USA;(2) Department of Neuropathology, University of Rochester, Rochester, NY, USA;(3) James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA; |
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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. |
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