Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.
Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.
Int J Mol Sci. 2019 Jan 8;20(1):226. doi: 10.3390/ijms20010226.
Laminin (Ln)-332 consists of α3, β3, and γ2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-γ2, a component of Ln-332, is frequently expressed as a monomer in the invasion front of several types of malignant tissues without simultaneous expression of Ln-α3 and/or Ln-β3 chains. Moreover, monomeric Ln-γ2 induces tumor cell proliferation and migration in vitro. These unique biological activities indicate that monomeric Ln-γ2 could be a candidate biomarker for early cancer surveillance. However, the present immune method for monomeric Ln-γ2 detection can only predict its expression, since no antibody that specifically reacts with monomeric γ2, but not with heterotrimeric γ2 chain, is commercially available. We have, therefore, developed monoclonal antibodies to specifically detect monomeric Ln-γ2, and devised a highly sensitive method to measure serum monomeric Ln-γ2 levels using a fully automated chemiluminescent immunoassay (CLIA). We evaluated its diagnostic value in sera from patients with several digestive cancers, including hepatocellular carcinoma (HCC), and found serum monomeric Ln-γ2 to be a clinically available biomarker for HCC surveillance. The combination of monomeric Ln-γ2 and prothrombin induced by Vitamin K Absence II (PIVKA-II) may be more sensitive for clinical diagnosis of HCC than any currently used combination.
层粘连蛋白 (Ln)-332 由α3、β3 和γ2 链组成，介导上皮细胞与基底膜的黏附。Ln-γ2 是 Ln-332 的一个组成部分，在几种类型的恶性组织的侵袭前沿常以单体形式表达，而不同时表达 Ln-α3 和/或 Ln-β3 链。此外，单体 Ln-γ2 可诱导肿瘤细胞在体外增殖和迁移。这些独特的生物学活性表明，单体 Ln-γ2 可能是早期癌症监测的候选生物标志物。然而，目前用于单体 Ln-γ2 检测的免疫方法只能预测其表达，因为没有可特异性识别单体γ2 而不识别异三聚体γ2 链的抗体可供商业使用。因此，我们开发了针对单体 Ln-γ2 的单克隆抗体，并设计了一种使用全自动化学发光免疫分析 (CLIA) 高度敏感地测量血清单体 Ln-γ2 水平的方法。我们评估了其在几种消化系统癌症（包括肝细胞癌 (HCC)）患者血清中的诊断价值，并发现血清单体 Ln-γ2 是 HCC 监测的一种临床可用的生物标志物。单体 Ln-γ2 与维生素 K 缺乏 II 诱导的凝血酶原 (PIVKA-II) 的组合可能比目前任何使用的组合更敏感，用于 HCC 的临床诊断。
