title: 3β-hydroxysterol δ24-reductase on the surface of hepatitis C virus-related hepatocellular carcinoma cells can be a target for molecular targeting therapy.
abstract: In our previous study, we demonstrated that 3β-hydroxysterol Δ24-reductase (DHCR24) was overexpressed in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), and that its expression was induced by HCV. Using a monoclonal antibody against DHCR24 (2-152a MAb), we found that DHCR24 was specifically expressed on the surface of HCC cell lines. Based on these findings, we aimed to establish a novel targeting strategy using 2-152a MAb to treat HCV-related HCC. In the present study, we examined the antitumor activity of 2-152a MAb. In the presence of complement, HCC-derived HuH-7 cells were killed by treatment with 2-152a MAb, which was mediated by complement-dependent cytotoxicity (CDC). In addition, the antigen recognition domain of 2-152a MAb was responsible for the unique anti-HCV activity. These findings demonstrate the feasibility of using 2-152a MAb for antibody therapy against HCV-related HCC. In addition, surface DHCR24 on HCC cells exhibited a functional property, agonist-induced internalization. We showed that 2-152a MAb-mediated binding of a cytotoxic agent (a saponin-conjugated secondary antibody) to surface DHCR24 led to significant cytotoxicity. This suggests that surface DHCR24 on HCC cells can function as a carrier for internalization. Therefore, surface DHCR24 could be a valuable target for HCV-related HCC therapy, and 2-152a MAb appears to be useful for this targeted therapy.
authors: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto-City, Kumamoto, Japan; Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, Japan.
authors: Makoto
authors: M
authors: Saito
authors: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto-City, Kumamoto, Japan; Division of Veterinary Public Health, Nippon Veterinary and Life Science University, 1-7-1 Kyonan, Musashino, Tokyo, Japan.
authors: Takashi
authors: T
authors: Takano
authors: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto-City, Kumamoto, Japan; Chemo-Sero-Therapeutic Research Institute, Kikuchi Research Center, Kyokushi, Kikuchi, Kumamoto, Japan.
authors: Tomohiro
authors: T
authors: Nishimura
authors: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, Japan.
authors: Michinori
authors: M
authors: Kohara
authors: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto-City, Kumamoto, Japan; Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 1-21-24 Korimoto, Kagoshima, Japan; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 1-21-24 Korimoto, Kagoshima, Japan.
authors: Kyoko
authors: K
authors: Tsukiyama-Kohara
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000201:enzymology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human