Yin Haoyuan, Shao Ying, Chen Xuan
Department of Neurovascular Surgery, The First Hospital of Jilin University, No71 Xinmin Road, Changchun, Jilin, 130021, China.
Department of Plastic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Neurol Sci. 2017 Jan;38(1):129-136. doi: 10.1007/s10072-016-2727-2. Epub 2016 Oct 19.
To analyze the effects of extracellular matrix metalloproteinase inducer (CD147) on glioma proliferation, apoptosis, invasion, and angiogenesis. Tissue samples were obtained from 101 glioma cases while normal brain tissues were obtained from 30 brain injury cases. Immunohistochemical assay was performed to detect the expressions of CD147, CD34, and VEGF in tissue samples. QRT-PCR was performed to detect the relative expression of CD147 mRNA in human glioma cell lines. CD147 siRNA was transfected into glioma cell line U251. Cell proliferation, apoptosis, invasion, and angiogenesis were tested by MTT, flow cytometry, Transwell assay, and vasculogenic mimicry assay, respectively. Expressions of relative proteins were analyzed with western blot. CD147 was positively expressed with the percentage of 0, 37.5, 44.8, 67.9, and 85.7 % in normal tissues and glioma tissues with WHO grades I-IV, respectively, and the scores of MVDand VEGF were associated with the expression of CD147. CD147 was significantly upregulated in the human glioma cell lines (P < 0.05). Downregulated the expression of CD147 suppressed cell proliferation, blocked cell cycle, induced apoptosis, inhibited cell invasion and angiogenesis in glioma cells in vitro. The expression of CD147 was significantly associated with WHO tumor grade and angiogenesis; silencing of CD147 contributed to inhibition of glioma proliferation, invasion, and angiogenesis. Our study provided firm evidence that CD 147 is a potential glioma target for anti-angiogenic therapies.
分析细胞外基质金属蛋白酶诱导剂(CD147)对胶质瘤增殖、凋亡、侵袭和血管生成的影响。收集101例胶质瘤组织样本,同时收集30例脑损伤患者的正常脑组织样本。采用免疫组织化学法检测组织样本中CD147、CD34和VEGF的表达。采用实时荧光定量PCR法检测人胶质瘤细胞系中CD147 mRNA的相对表达量。将CD147小干扰RNA转染至胶质瘤细胞系U251。分别采用MTT法、流式细胞术、Transwell小室实验和血管生成拟态实验检测细胞增殖、凋亡、侵袭和血管生成情况。采用蛋白质免疫印迹法分析相关蛋白的表达。CD147在正常组织和WHO分级I-IV级胶质瘤组织中的阳性表达率分别为0、37.5%、44.8%、67.9%和85.7%,微血管密度和VEGF评分与CD147的表达相关。CD147在人胶质瘤细胞系中显著上调(P<0.05)。下调CD147的表达可抑制体外胶质瘤细胞的增殖、阻断细胞周期、诱导凋亡、抑制细胞侵袭和血管生成。CD147的表达与WHO肿瘤分级和血管生成显著相关;沉默CD147有助于抑制胶质瘤的增殖、侵袭和血管生成。我们的研究提供了确凿证据,表明CD147是抗血管生成治疗潜在的胶质瘤靶点。