Jeng Kuo-Shyang, Sheen I-Shyan, Lin Shu-Sheng, Leu Chuen-Miin, Chang Chiung-Fang
Division of General Surgery, Far Eastern Memorial Hospital, New Taipei 22060, Taiwan.
Department of Hepatogastroenterology, Chang-Gung Memorial Hospital, Linkou Medical Center, Chang-Gung University, Taoyuan City 33305, Taiwan.
Int J Mol Sci. 2021 Mar 22;22(6):3208. doi: 10.3390/ijms22063208.
Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.
内皮糖蛋白（CD105）是一种I型整合跨膜糖蛋白，也是转化生长因子-β（TGF-β）配体的共受体。内皮糖蛋白/TGF-β信号通路调节止血、细胞增殖/迁移、细胞外基质（ECM）合成和血管生成。血管生成在全球最常见的恶性肿瘤之一肝细胞癌（HCC）的早期进展、侵袭、术后复发和转移中起作用。内皮糖蛋白在新形成的HCC微血管中过度表达。它增加了肝硬化和再生性HCC结节中的微血管密度。此外，HCC患者体内存在循环内皮糖蛋白，提示其有作为诊断或预后因素的潜力。HCC血管生成是动态的，内皮糖蛋白表达随阶段而异。TRC105（卡妥昔单抗）是一种抗内皮糖蛋白抗体，其三项临床试验与肝脏疾病有关。TRC105与索拉非尼联合使用时取得了部分缓解。尽管抗血管生成治疗仍有一些风险，但内皮糖蛋白抑制剂或其他靶向治疗的联合治疗具有前景。
