Department of Histology and Embryology, University of Medical Sciences, Poznań 60-781, Poland.
Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, University of Medical Sciences, Poznań 61-285, Poland.
Int J Mol Sci. 2018 Dec 5;19(12):3887. doi: 10.3390/ijms19123887.
The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-related mortality worldwide. HCC is characterized by its hypervascularization. Improving the efficiency of anti-angiogenic treatment and mitigation of anti-angiogenic drug resistance are the top priorities in the development of non-surgical HCC therapies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factor β (TGF-β) co-receptors. Involvement of that protein in angiogenesis of solid tumours is well documented. Endoglin is a marker of activated endothelial cells (ECs), and is preferentially expressed in the angiogenic endothelium of solid tumours, including HCC. HCC is associated with changes in CD105-positive ECs within and around the tumour. The large spectrum of endoglin effects in the liver is cell-type- and HCC- stage-specific. High expression of endoglin in non-tumour tissue suggests that this microenvironment might play an especially important role in the progression of HCC. Evaluation of tissue expression, as well as serum concentrations of this glycoprotein in HCC, tends to confirm its role as an important biomarker in HCC diagnosis and prognosis. The role of endoglin in liver fibrosis and HCC progression also makes it an attractive therapeutic target. Despite these facts, the exact molecular mechanisms of endoglin functioning in hepatocarcinogenesis are still poorly understood. This review summarizes the current data concerning the role and signalling pathways of endoglin in hepatocellular carcinoma development and progression, and provides an overview of the strategies available for a specific targeting of CD105 in anti-angiogenic therapy in HCC.
肝脏同时接受动脉和静脉血液灌注，导致异常的微环境选择更具侵袭性的恶性肿瘤。肝细胞癌 (HCC) 是最常见的原发性肝癌，是全球第六大常见癌症，也是全球癌症相关死亡的第三大主要原因。HCC 的特征是其高血管生成。提高抗血管生成治疗的效率和减轻抗血管生成药物耐药性是开发非手术 HCC 治疗方法的首要任务。内皮糖蛋白 (CD105) 是一种跨膜糖蛋白，是转化生长因子 β (TGF-β) 的共受体之一。该蛋白参与实体瘤的血管生成已有充分的文献记载。Endoglin 是激活的内皮细胞 (ECs) 的标志物，在包括 HCC 在内的实体瘤的血管生成内皮中优先表达。HCC 与肿瘤内和周围 CD105 阳性 EC 的变化有关。Endoglin 在肝脏中的作用具有广泛的谱，且具有细胞类型和 HCC 分期特异性。非肿瘤组织中 endoglin 的高表达表明该微环境可能在 HCC 的进展中发挥特别重要的作用。评估组织表达以及 HCC 中该糖蛋白的血清浓度往往可以证实其在 HCC 诊断和预后中的重要生物标志物作用。Endoglin 在肝纤维化和 HCC 进展中的作用也使其成为有吸引力的治疗靶点。尽管如此，endoglin 在肝癌发生中的作用的确切分子机制仍知之甚少。这篇综述总结了有关 endoglin 在肝细胞癌发生和发展中的作用和信号通路的最新数据，并概述了针对 CD105 在 HCC 抗血管生成治疗中特异性靶向的可用策略。
