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01-01-2015 | Research Paper

A chimeric antibody targeting CD147 inhibits hepatocellular carcinoma cell motility via FAK-PI3K-Akt-Girdin signaling pathway

Authors: Yuan Wang, Lin Yuan, Xiang-Min Yang, Ding Wei, Bin Wang, Xiu-Xuan Sun, Fei Feng, Gang Nan, Ye Wang, Zhi-Nan Chen, Huijie Bian

Published in: Clinical & Experimental Metastasis | Issue 1/2015

Abstract

CD147 is expressed at low levels in normal tissues but frequently highly expressed in a wide range of tumor types such as lung, breast, and liver and therefore it is a potentially unique therapeutic target for these diverse tumor types. We previously generated a murine antibody HAb18 which suppresses matrix met al.loproteinase-2 and matrix metalloproteinase-9 secretion, attenuates cell invasion by blocking the CD147 molecule in tumor cells. Here, we generated a chimeric antibody containing the variable heavy and variable light chains of murine HAb18 and the constant regions of human IgG1γ1 and human κ chain as a potential therapeutic agent (designated cHAb18). Quantitative measurement of cHAb18 antibody affinity for antigen CD147 with surface plasmon resonance showed the equilibrium dissociation constant K_D was 2.66 × 10⁻¹⁰ mol/L, similar to that of K_D 2.73 × 10⁻¹⁰ mol/L for murine HAb18. cHAb18 induced antibody-dependent cell-mediated cytotoxicity in two hepatocellular carcinoma cell lines, SMMC-7721 and Huh-7 cells. It inhibited cancer invasion and migration in hepatocellular carcinoma cells by specifically blocking CD147. Except for the depression of matrix metalloproteinase-2 and matrix metalloproteinase-9 expressions, cHAb18 antibody suppressed cell motility by rearrangement of actin cytoskeleton, which was probably induced by decreasing the phosphorylation of focal adhesion kinase, phosphatidylinositide-3 kinase (PI3K), Akt, and Girdin in the integrin signaling pathway. In an orthotopic model of hepatocellular carcinoma in BALB/c nude mice, cHAb18 treatment effectively reduced the tumor metastasis in liver and prolonged the survival. These findings reveal new therapeutic potential for cHAb18 antibody targeting CD147 on tumor therapy.

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Title: A chimeric antibody targeting CD147 inhibits hepatocellular carcinoma cell motility via FAK-PI3K-Akt-Girdin signaling pathway
Authors: Yuan Wang
Lin Yuan
Xiang-Min Yang
Ding Wei
Bin Wang
Xiu-Xuan Sun
Fei Feng
Gang Nan
Ye Wang
Zhi-Nan Chen
Huijie Bian
Publication date: 01-01-2015
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 1/2015
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-014-9689-7

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