Reference - Detail
RRC ID | 57436 |
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Author | Saito M, Takano T, Nishimura T, Kohara M, Tsukiyama-Kohara K. |
Title | 3β-hydroxysterol δ24-reductase on the surface of hepatitis C virus-related hepatocellular carcinoma cells can be a target for molecular targeting therapy. |
Journal | PLoS One |
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. |
Volume | 10(4) |
Pages | e0124197 |
Published | 2015-1-1 |
DOI | 10.1371/journal.pone.0124197 |
PII | PONE-D-14-57568 |
PMID | 25875901 |
PMC | PMC4395381 |
MeSH | Antibodies, Monoclonal / pharmacology* Blotting, Western Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / enzymology Carcinoma, Hepatocellular / etiology Cell Proliferation Enzyme-Linked Immunosorbent Assay Flow Cytometry Hepacivirus / physiology* Hepatitis C, Chronic / complications* Hepatitis C, Chronic / enzymology Hepatitis C, Chronic / virology Humans Liver Neoplasms / drug therapy* Liver Neoplasms / enzymology Liver Neoplasms / etiology Molecular Targeted Therapy Nerve Tissue Proteins / antagonists & inhibitors* Nerve Tissue Proteins / immunology Nerve Tissue Proteins / metabolism Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors* Oxidoreductases Acting on CH-CH Group Donors / immunology Oxidoreductases Acting on CH-CH Group Donors / metabolism Tumor Cells, Cultured Virus Replication / drug effects* |
IF | 2.776 |
Times Cited | 4 |
Resource | |
DNA material | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |