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::Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA level...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9547-4
更新日期:2013-04-01 00:00:00
abstract::To evaluate the relationship between the c-kit proto-oncogene product and malignant transformation of human breast tissue, we examined the immunohistochemical expression of the c-kit proto-oncogene product in both malignant and non-malignant breast tissues. The immunohistochemical expression of the c-kit proto-oncogen...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1027323210736
更新日期:2003-01-01 00:00:00
abstract::The milieu of the liver, and in particular hepatocyte-derived extracellular matrix (hECM), is a critical factor regulating development of liver metastases of colorectal cancer (CRC) cells. The present study has investigated genes altered by hECM in CRC cells and particularly by heparan sulfate chains of hepatocyte pro...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9527-8
更新日期:2013-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00133483
更新日期:1995-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-1198-2
更新日期:2004-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1016395316362
更新日期:2002-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00117932
更新日期:1986-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9482-4
更新日期:2012-12-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9080-z
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9099-1
更新日期:2008-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01769359
更新日期:1991-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006580406314
更新日期:1998-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1025461507027
更新日期:2003-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9469-1
更新日期:2012-08-01 00:00:00
abstract::Emerging evidence suggests that gap junctional intercellular communication (GJIC) and expression of connexins (Cx) contribute to the metastatic potential of breast cancer cells. To more directly address this, an aggressive bone metastasis breast cancer cell line, MDA-MET (MET), was stably transfected with human Cx43 c...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9140-4
更新日期:2008-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01784377
更新日期:1988-11-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-006-9032-z
更新日期:2006-01-01 00:00:00
abstract::Repeated administration of the hepatic lectin blocking agents D-galactose or arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic ESb lymphoma cells of the liver of DBA/2 mice. Therefore,...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01784842
更新日期:1988-03-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1013186331662
更新日期:2000-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9064-z
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9135-1
更新日期:2008-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-007-9123-5
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9260-0
更新日期:2009-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-3098-x
更新日期:2005-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9461-9
更新日期:2012-06-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006502009682
更新日期:1998-11-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1020923326441
更新日期:2002-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
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更新日期:2018-08-01 00:00:00