Yan H P, Roberts L J, Davies S S, Pohlmann P, Parl F F, Estes S, Maeng J, Parker B, Mernaugh R
Department of Radiation Oncology at Washington University in St. Louis, Washington 63110, United States.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Free Radic Biol Med. 2017 May;106:62-68. doi: 10.1016/j.freeradbiomed.2017.02.020. Epub 2017 Feb 9.
The cellular production of free radicals or reactive oxygen species (ROS) can lead to protein, lipid or DNA modifications and tumor formation. The cellular lipids undergo structural changes through the actions of enzymes (e.g. cyclooxygenases) or free radicals to form a class of compounds called Isolevuglandins (IsoLGs). The recruitment and continued exposure of tissue to ROS and IsoLGs causes increased cell proliferation, mutagenesis, loss of normal cell function and angiogenesis. The elevated concentration of ROS in cancerous tissues suggests that these mediators play an important role in cancer development. We hypothesized that tumors with elevated ROS levels would similarly possess an increased concentration of IsoLGs when compared with normal tissue. Using D11, an ScFv recombinant antibody specific for IsoLGs, we utilized immunohistochemistry to visualize the presence of IsoLG in human tumors compared to normal adjacent tissue (NAT) to the same tumor. We found that IsoLG concentrations were elevated in human breast, colon, kidney, liver, lung, pancreatic and tongue tumor cells when compared to NAT and believe that IsoLGs can be used as a gauge indicative of lipid peroxidation in tumors.
细胞产生自由基或活性氧(ROS)可导致蛋白质、脂质或DNA修饰以及肿瘤形成。细胞脂质通过酶(如环氧化酶)或自由基的作用发生结构变化,形成一类称为异左旋葡聚糖(IsoLGs)的化合物。组织对ROS和IsoLGs的募集及持续暴露会导致细胞增殖增加、诱变、正常细胞功能丧失和血管生成。癌组织中ROS浓度升高表明这些介质在癌症发展中起重要作用。我们假设,与正常组织相比,ROS水平升高的肿瘤同样会有更高浓度的IsoLGs。使用D11(一种对IsoLGs特异的单链抗体片段重组抗体),我们利用免疫组织化学方法,将同一肿瘤的人肿瘤组织与其相邻正常组织(NAT)进行比较,以观察IsoLG在人肿瘤中的存在情况。我们发现,与NAT相比,人乳腺、结肠、肾、肝、肺、胰腺和舌肿瘤细胞中的IsoLG浓度升高,并且认为IsoLGs可作为肿瘤脂质过氧化的一个指示指标。