Li Xiaoxiang, Ji Zhenwei, Ma Yunlei, Qiu Xiuchun, Fan Qingyu, Ma Baoan
Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Shaanxi 710038, P.R. China.
Oncol Lett. 2012 Jun;3(6):1268-1274. doi: 10.3892/ol.2012.645. Epub 2012 Mar 15.
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.
据报道,缺氧诱导因子-1α(HIF-1α)可反式激活血管内皮生长因子(VEGF)和基质金属蛋白酶-2(MMP-2)的表达,这两种因子在多种癌症中常过度表达,且已知是血管生成的重要调节因子。很少有研究调查这些因子在实体瘤中的作用,尤其是脊索瘤,这是一种罕见的肿瘤,被认为起源于脊索残余。为了阐明HIF-1α是否参与脊索瘤组织中的血管生成,我们使用包含35个脊索瘤样本的组织芯片,通过免疫组织化学检测了HIF-1α、VEGF和MMP-2的表达。结果表明,大多数脊索瘤样本中都表达HIF-1α、VEGF和MMP-2。VEGF表达与HIF-1α和MMP-2表达以及微血管密度(MVD)显著相关。然而,脊索瘤患者的预后与这些因子的表达无显著关联,但与MVD相关。因此,结果表明脊索瘤中HIF-1α、VEGF和MMP-2的表达之间存在相关性,并且血管生成过程是脊索瘤的一个潜在治疗靶点。