Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and matrix metalloproteinase-2 in sacral chordomas

Abstract

Abstract. Hypoxia-inducible factor-1α (HIF-1α) has been reported to transactivate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2), which are frequently overexpressed in numerous types of cancer and are known to be significant regulators of angiogenesis. Few studies have investigated the role of these factors in solid tumors, particularly chordomas, which are rare tumors that are thought to originate from notochordal remnants. To clarify whether HIF-1α is involved in angiogenesis in chordoma tissues, we examined the expression of HIF-1α, VEGF and MMP-2 with immunohistochemistry using a tissue microarray containing 35 chordoma samples. The results indicated that HIF-1α, VEGF and MMP-2 are expressed in the majority of chordoma samples. VEGF expression was significantly correlated with HIF-1α and MMP-2 expression, as well as with microvessel density (MVD). However, the prognosis of the chordoma patients was not significantly associated with the expression of these factors, but was associated with MVD. The results therefore showed that there is a correlation between the expression of HIF-1α, VEGF and MMP-2 in chordomas and that the angiogenic process is a potential therapeutic target for chordomas.

Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing

“…The mutation had already been reported previously in chordoma and is supposed to be tolerated 13 . According to the literature, VEGF has been shown to be expressed in 77.8% of 28 sacral chordomas 17 , 18 . Akhavan-Sigari et al 2013 19 reported low expression of VEGFR-2 in 145 clivus chordomas, yet high expression of VEGFR-2 was correlated with a poor prognosis in their samples.…”

Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO)

“…Chordomas inconstantly express some actionable targets, mainly stem-cell factor receptor (c-KIT), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), receptor tyrosine-protein kinase erbB-2 (HER2/neu) and epidermal growth factor receptor (EGFR) [ 1 , 6 , 7 ]. Li et al [ 8 ] and Chen et al [ 9 ] found high levels of VEGF expression in 71% (25/35) and 77.8% (28/36) of chordomas, respectively.…”

Investigating Microenvironmental Regulation of Human Chordoma Cell Behaviour

“…However, under hypoxic conditions, HIF-1α becomes stabilized, translocates to the nucleus, and dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT) binding to the HIF-1 consensus sequence to activate hypoxia-inducible genes. Recent studies have reported HIF-1α expression in the majority of chordoma samples examined, correlated with VEGF expression and tumour microvessel density [18] , [71] . While we did not detect the induction of HIF1A gene expression in U-CH1 cells maintained in hypoxia, we detected a significant up-regulation of VEGF-A and GLUT1 gene expression, suggesting increased HIF-1α activity in hypoxia.…”

“…For example, under hypoxia prostate cancer cells show increased cell proliferation [15] , and prostate [15] , breast [16] and colon [17] cancer cells display increased migration compared to cells cultured under normoxia. In addition, studies have shown that hypoxia can promote stem and progenitor cell properties in various cancers including glioma, glioblastoma and ovarian cancer [18] , [19] .…”