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Int. J. Mol. Sci. 2019, 20(1), 226; https://doi.org/10.3390/ijms20010226

Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review

1
Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan
2
Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan
3
Diagnostics Division, Abbott Japan Co., Ltd., Chiba 270-2214, Japan
4
Division of Cancer Cell Research, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
5
Faculty of Medicine, Institute of Medical, Pharmaceutical & Health Science, Kanazawa University, Takara-machi, Kanazawa 920-0934, Japan
*
Authors to whom correspondence should be addressed.
Received: 15 November 2018 / Revised: 24 December 2018 / Accepted: 2 January 2019 / Published: 8 January 2019
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Abstract

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. View Full-Text
Keywords: hepatocellular carcinoma; monomeric laminin-γ2; biomarker; α-fetoprotein; prothrombin induced by Vitamin K Absence II; surveillance hepatocellular carcinoma; monomeric laminin-γ2; biomarker; α-fetoprotein; prothrombin induced by Vitamin K Absence II; surveillance
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Yasuda, H.; Nakagawa, M.; Kiyokawa, H.; Yoshida, E.; Yoshimura, T.; Koshikawa, N.; Itoh, F.; Seiki, M. Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review. Int. J. Mol. Sci. 2019, 20, 226.

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