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

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 immunohisto-chemistry 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

Impact of somatic copy number alterations on the glioblastoma miRNome: miR‐4484 is a genomically deleted tumour suppressor

“…PXDN, yet another putative gene target of miR‐4484, is an adhesion biomolecule which functions as an important regulator of cellular plasticity and extracellular matrix remodelling. PXDN levels were found to be elevated in primary glial and secondary metastatic brain tumours as well as in its immediate microvasculature (Liu et al ., 2010). Similarly, ITGB1, a cell adhesive molecule, which functions to mediate association between cells and the ECM, has also been found to be misregulated in various cancers and found to impact malignant phenotypes such as invasion, proliferation and angiogenesis (He et al ., 2016; Zhang and Zou, 2015).…”

Multidomain Human Peroxidasin 1 Is a Highly Glycosylated and Stable Homotrimeric High Spin Ferric Peroxidase

“…In the following 15 years, only a few papers were published reporting the occurrence of peroxidasins in other organisms like Caenorhabditis elegans (5) or Xenopus tropicalis (6) and suggesting a role in extracellular matrix biosynthesis. Finally, in 2008, the two human peroxidasins (hsPxd01 and hsPxd02) became the focus of investigations analyzing expression patterns (7)(8)(9)(10) and biochemical properties (7,8,11,12).…”

Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis

“…26 PXDN was weakly expressed in normal brain tissue and was upregulated in the microvasculature and glioma endothelial cells of primary glial and metastatic brain tumors. 27 Expression has also been demonstrated in several other tumor types including melanoma, breast, ovarian, colon and renal cell cancer. 28,29 PXDN encodes peroxidasin, a protein that is located in the endoplasmic reticulum and secreted into the extracellular space.…”