Unique Biological Activity and Potential Role of Monomeric Laminin-2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review

Laminin (Ln)-332 consists of 3, 3, and 2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-2, 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-3 and/or Ln-3 chains. Moreover, monomeric Ln-2 induces tumor cell proliferation and migration in vitro. These unique biological activities indicate that monomeric Ln-2 could be a candidate biomarker for early cancer surveillance. However, the present immune method for monomeric Ln-2 detection can only predict its expression, since no antibody that specifically reacts with monomeric 2, but not with heterotrimeric 2 chain, is commercially available. We have, therefore, developed monoclonal antibodies to specifically detect monomeric Ln-2, and devised a highly sensitive method to measure serum monomeric Ln-2 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-2 to be a clinically available biomarker for HCC surveillance. The combination of monomeric Ln-2 and prothrombin induced by Vitamin K Absence II (PIVKA-II) may be more sensitive for clinical diagnosis of HCC than any currently used combination.