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 KD was 2.66 × 10(-10) mol/L, similar to that of KD 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.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Wang Y,Yuan L,Yang XM,Wei D,Wang B,Sun XX,Feng F,Nan G,Wang Y,Chen ZN,Bian Hdoi
10.1007/s10585-014-9689-7subject
Has Abstractpub_date
2015-01-01 00:00:00pages
39-53issue
1eissn
0262-0898issn
1573-7276journal_volume
32pub_type
杂志文章abstract::Although in the past little attention has been paid to the influence of osteosarcoma cells in osteoclast function, recent studies suggest a close relationship between osteosarcoma aggressiveness and osteoclastic activity. The present study addresses the paracrine effects of MG63 cells, a human osteosarcoma-derived cel...
journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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doi:10.1007/BF00132306
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journal_title:Clinical & experimental metastasis
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更新日期:2016-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
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doi:10.1023/a:1025883129932
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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更新日期:2012-04-01 00:00:00
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journal_title:Clinical & experimental metastasis
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doi:10.1007/s10585-009-9260-0
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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