來自第四軍醫(yī)大學腫瘤生物學國家重點實驗室的研究人員發(fā)現了我國首個新型通用癌生物標志物：HAb18G/CD147,，這一標志物作為癌癥的全新藥靶，對臨床診斷和預后判斷具有重要意義,。這一研究成果公布在《致癌基因》（Oncogene）,，《生物科學與生物工程期刊》（J Biosci Bioeng.）等雜志上。
領導這一研究的是第四軍醫(yī)大學陳志南院士,，陳志南院士在腫瘤轉移相關分子相互作用的分子調控網絡研究,、粘附分子HAb18G/CD147與整合素家族及AnnexinⅡ相互作用參與肝癌細胞的侵襲轉移、HAb18G/CD147分子通過調節(jié)EMT現象參與腫瘤發(fā)生,、HAb18G/CD147剪接異構體與結構生物學研究,、癌基因組與個體化醫(yī)學研究、細胞周期與腫瘤生物學等相關基礎及應用基礎研究方面取得重要進展,。
據報道,，為了能探討綜合治療癌癥的新方法，陳志南院士研究組開拓思路,，高起點地選擇了肝癌單抗藥靶分子的研究及抗炎,、抗病毒功能、肝癌移植抗復發(fā)治療等多層面的研究,，經反復檢測實驗,，他們終于成功研制出HAb18G/CD147拮抗劑（利卡汀）,。經對各類癌組織的28組組織芯片,、1252個樣品點,、1117例乳腺癌病理標本進行組織學和血清學檢測，結果顯示：HAb18G/CD147對良性瘤不表達,，對癌表達率為66.6%,，能使肝癌移植治療一年復發(fā)率降低30.4%，患者生存率提高24.7%,，這表明HAb18G/CD147是一個新型通用,、有較好特異性、與癌癥發(fā)生發(fā)展密切相關的標志物,，為癌癥的早期預警,、病理分型、分期診斷,、預后判斷有著重要的應用價值,。
研究還發(fā)現，HAb18G/CD147對抗類風濕關節(jié)炎（RA）,、SARS,、HIV-1等病毒性疾病，具有良好的抗炎,、抑制作用,，是一個新型穩(wěn)定的治療藥靶。在此基礎上,，他們研發(fā)出具有我國自主知識產權的HAb18G/CD147癌癥標志物免疫組化診斷試劑盒,，并獲得PCT國際專利授權1項和國家頒發(fā)的知識產權專利證書及生產許可證書。目前這一試劑盒已投入批量生產,。
這項研究由于涉及相關產業(yè),，因此引發(fā)了爭議，據羊城晚報報道,，媒體報道的HAb18G/CD147癌癥標志物免疫組化診斷試劑盒,，不涉及公司和第四軍醫(yī)大學關于《碘【131I】-HAb18肝癌單克隆抗體注射液技術轉讓合同書》的技術轉讓范疇。目前公司產品利卡汀僅用于治療原發(fā)性肝癌,，其對公司業(yè)績暫難評估,。（生物谷Bioon.com）
生物谷推薦原文出處：
Oncogene DOI： 10.1038/onc.2011.149
HAb18G/CD147 promotes epithelial-mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug.
Wu J,Ru N-Y NY,Zhang Y,Li Y,Wei D,Ren Z,Huang XF,Chen ZN,Bian H
Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β (TGF-β) is implicated in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, which belongs to the CD147 family, is an HCC-associated antigen that has a crucial role in tumor invasion and metastasis. The goal of this study was to investigate the role of HAb18G/CD147 during EMT in hepatocarcinogenesis. Human normal hepatic cell lines QZG and L02, primary mouse hepatocytes and nude mouse models were used to determine the role of HAb18G/CD147 in EMT, and the involvement of the TGF-β-driven pathway. A dual-luciferase reporter assay and ChIP were used to investigate the transcriptional regulation of the CD147 gene. Samples from patients with liver disease were assessed to determine the relationship between HAb18G/CD147 and typical markers for EMT. Our results show that upregulation of HAb18G/CD147 is induced by TGF-β coupled with downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The expression of HAb18G/CD147 is controlled by the cell survival PI3K/Akt/GSK3β signaling pathway, and is directly regulated by the transcription factor Slug. Transfection of CD147 also induces an elevated expression of TGF-β. CD147-transfected hepatocytes have mesenchymal phenotypes that accelerate tumor formation and tumor metastasis in vivo. Immunohistochemistry analysis shows a negative correlation between HAb18G/CD147 and E-cadherin expression (r(s)=-0.3622, P=0.0105), and a positive correlation between HAb18G/CD147 and Slug expression (r(s)=0.3064, P=0.0323) in human HCC tissues. Our study uncovers a novel role of HAb18G/CD147 in mediating EMT in the process of HCC progression and showed that CD147 is a Slug target gene in the signaling cascade TGF-β→PI3K/Akt→GSK3β→Snail→Slug→CD147. Our results suggest that CD147 may be a potential target for the treatment and prevention of HCC.
