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


: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.


Clin Exp Metastasis


Wang Y,Yuan L,Yang XM,Wei D,Wang B,Sun XX,Feng F,Nan G,Wang Y,Chen ZN,Bian H




Has Abstract


2015-01-01 00:00:00












  • Cathepsin L inhibition by the small molecule KGP94 suppresses tumor microenvironment enhanced metastasis associated cell functions of prostate and breast cancer cells.

    abstract::Metastasis remains the major cause of therapeutic failure, poor prognosis and high mortality in breast and prostate cancer patients. Aberrant microenvironments including hypoxia and acidic pH are common features of most solid tumors that have been long associated with enhanced metastasis and poor patient outcomes. Nov...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Sudhan DR,Siemann DW

    更新日期:2013-10-01 00:00:00

  • Human and rat glioma growth, invasion, and vascularization in a novel chick embryo brain tumor model.

    abstract::The mechanisms that control the insidiously invasive nature of malignant gliomas are poorly understood, and their study would be facilitated by an in vivo model that is easy to manipulate and inexpensive. The developing chick embryo brain was assessed as a new xenograft model for the production, growth, and study of h...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Cretu A,Fotos JS,Little BW,Galileo DS

    更新日期:2005-01-01 00:00:00

  • Treatment with human recombinant leukocyte interferons inhibits in vitro invasive ability of human lung carcinoma cells.

    abstract::The effects of treatment of human lung carcinoma cell line A 549 with recombinant DNA-derived human leukocyte interferons A (rIFN-alpha A) or D (rIFN-alpha D), and human lymphoblastoid interferon (Wellferon) on in vitro cell invasion were investigated in a quantitative invasion assay using human amnion. The A 549 cell...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Ravine TJ,Ledinko N

    更新日期:1986-07-01 00:00:00

  • CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival.

    abstract::Cancer cells with the surface marker profile CD44+/CD24- have previously been described to possess cancer stem cell-like properties. This manuscript evaluates those properties in ovarian cancer cell lines. The proportion of CD44+/CD24- cells corresponded to the clinical aggressiveness of each ovarian cancer cell line ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Meng E,Long B,Sullivan P,McClellan S,Finan MA,Reed E,Shevde L,Rocconi RP

    更新日期:2012-12-01 00:00:00

  • Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma.

    abstract::The exact cellular and molecular mechanisms involved in melanoma tumorigenesis remain obscure. Previous gene expression profiling analyses performed upon NHEM and human melanoma samples identified WFDC1 as one of the most frequently down-regulated genes. Here we further showed that NHEM readily express WFDC1 but expre...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Liu S,Howell P,Ren S,Fodstad O,Zhang G,Samant R,Shevde L,Xi Y,Pannell LK,Riker AI

    更新日期:2009-01-01 00:00:00

  • Increased lymphangiogenesis in lung metastases from colorectal cancer is associated with early lymph node recurrence and decreased overall survival.

    abstract::Pulmonary metastasectomy (PM) is an accepted treatment modality in colorectal cancer (CRC) patients with pulmonary tumor spread. Positive intrathoracic lymph nodes at the time of PM are associated with a poor prognosis and 5-year survival rates of <20 %. Increased lymphangiogenesis in pulmonary metastases might repres...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,多中心研究


    authors: Schweiger T,Nikolowsky C,Graeter T,Seebacher G,Laufer J,Glueck O,Glogner C,Birner P,Lang G,Klepetko W,Ankersmit HJ,Hoetzenecker K

    更新日期:2016-02-01 00:00:00

  • Naturally occurring resistance of bone marrow mononuclear and metastatic cancer cells to anticancer agents.

    abstract::Numerous cancer patients fail standard chemotherapy or develop resistance to chemotherapy during the course of treatment. The purpose of this study is to elucidate the overall response of cells obtained from cancer patients and from normal individuals to chemotherapeutic agents. We analysed the chemosensitivity of can...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Richard C,Yau J,Th'ng JP,Duivenvoorden WC

    更新日期:2006-01-01 00:00:00

  • Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan.

    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


    authors: Beuth J,Ko HL,Schirrmacher V,Uhlenbruck G,Pulverer G

    更新日期:1988-03-01 00:00:00

  • Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model.

    abstract::Sentinel lymph node (SLN) identification with preoperative image guidance may improve pathological staging of prostate cancer by identifying nodes outside the standard template of dissection. Four anesthetized male dogs received an intra-prostatic injection of Ga-68-labeled tilmanocept. Every 20 min the pelvic lymph n...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Stroup SP,Kane CJ,Farchshchi-Heydari S,James CM,Davis CH,Wallace AM,Hoh CK,Vera DR

    更新日期:2012-10-01 00:00:00

  • Transparent reporting of experimental parameters in assays measuring phenotypic steps in metastasis.

    abstract::Metastasis is key to cancer mortality. Understanding its biology is vital for developing strategies to prevent and treat metastasis. Phenotypic assays to either study metastasis or evaluate anti-metastatic drugs are widely used in preclinical research. This technical note discusses the adherence of reporting essential...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Boiy R,Steenbrugge J,Van Deun J,Hendrix A,Meyer E,De Wever O

    更新日期:2018-12-01 00:00:00

  • Role of the beta1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells.

    abstract::The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell-cell and cell-matrix interactions. We investigated the role of integrin subunits in ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Heyder C,Gloria-Maercker E,Hatzmann W,Niggemann B,Zänker KS,Dittmar T

    更新日期:2005-01-01 00:00:00

  • Assessment of methylation status of locoregional lymph nodes in lung cancer using EBUS-NA.

    abstract::Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationsh...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Millares L,Serra M,Andreo F,Sanz-Santos J,Montón C,Grimau C,Gallego M,Setó L,Combalia N,Llatjos M,Escoda R,Castellà E,Monsó E

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  • Role of extracellular matrix proteins in regulation of human glioma cell invasion in vitro.

    abstract::Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasio...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Chintala SK,Gokaslan ZL,Go Y,Sawaya R,Nicolson GL,Rao JS

    更新日期:1996-09-01 00:00:00

  • Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction.

    abstract::Platelet-derived growth factor BB (PDGF BB) and the PDGF receptor beta are expressed on mesothelioma cells, but their biological function has not yet been defined. In the present study we used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV or the non...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Klominek J,Baskin B,Hauzenberger D

    更新日期:1998-08-01 00:00:00

  • Therapeutic efficacy of two different cytostatic-linked phosphonates in combination with razoxane in the transplantable osteosarcoma of the rat.

    abstract::Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1- hydroxybutane-1,1-bisphosphonic acid (BAD) and aminotris-(methylenephosphonato)-diamminoplatinum(II) (ADP) that both have cytostatic and osteotropic properties, have shown good therapeutic efficacy against an osteosarcoma which metastasizes and kills by lu...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Klenner T,Wingen F,Keppler B,Valenzuela-Paz P,Amelung F,Schmähl D

    更新日期:1990-07-01 00:00:00

  • Sialylation of E-cadherin does not change the spontaneous or ET-18-OMe-mediated aggregation of MCF-7 human breast cancer cells.

    abstract::We have investigated the role of sialylation on cell-cell adhesion mediated by E-cadherin. Two MCF-7 human breast cancer cell variants were studied: MCF-7/AZ cells showed a spontaneous cell-cell adhesion in the fast and slow aggregation assay. whereas the adhesion deficient MCF-7/6 cell variant failed to form larger a...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Steelant WF,Recchi MA,Noë VT,Boilly-Marer Y,Bruyneel EA,Verbert A,Mareel MM,Delannoy P

    更新日期:1999-05-01 00:00:00

  • Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer.

    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


    authors: Okugawa Y,Inoue Y,Tanaka K,Kawamura M,Saigusa S,Toiyama Y,Ohi M,Uchida K,Mohri Y,Kusunoki M

    更新日期:2013-04-01 00:00:00

  • Combined effect of dehydroxymethylepoxyquinomicin and gemcitabine in a mouse model of liver metastasis of pancreatic cancer.

    abstract::Activation of nuclear factor-κB (NF-κB) has been implicated in metastasis of pancreatic cancer. We investigated the effects of the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on the inhibition of liver metastasis of pancreatic cancer in a mouse model of clinical liver metastasis. Nude mice were xenogr...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Suzuki K,Aiura K,Matsuda S,Itano O,Takeuchi O,Umezawa K,Kitagawa Y

    更新日期:2013-04-01 00:00:00

  • Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice.

    abstract::Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight f...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bar-Yehuda S,Farbstein T,Barer F,Ohana G,Fishman P

    更新日期:1999-01-01 00:00:00

  • Predicting brain metastases for non-small cell lung cancer based on magnetic resonance imaging.

    abstract::In this study the relationship between brain structure and brain metastases (BM) occurrence was analyzed. A model for predicting the time of BM onset in patients with non-small cell lung cancer (NSCLC) was proposed. Twenty patients were used to develop the model, whereas the remaining 69 were used for independent vali...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Yin G,Li C,Chen H,Luo Y,Orlandini LC,Wang P,Lang J

    更新日期:2017-02-01 00:00:00

  • Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis.

    abstract::Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This st...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Ji RC,Eshita Y,Kobayashi T,Hidano S,Kamiyama N,Onishi Y

    更新日期:2018-12-01 00:00:00

  • Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells.

    abstract::Anti-resorptive bisphosphonates (BPs) have been clinically used to prevent cancer-bone metastasis and cancer-induced bone pathologies despite the fact that the phenotypic response of the cancer-bone interactions to BP exposure is "uncharted territory". This study offers unique insights into the interplay between cance...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Alasmari A,Lin SC,Dibart S,Salih E

    更新日期:2016-08-01 00:00:00

  • Distinctive alterations of invasiveness, drug resistance and cell-cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant.

    abstract::Growth of human tumor cells as three-dimensional (3D) multicellular spheroids modifies their invasive properties. Here we study the differences in the biological features of MCF-7, a human breast cancer cell line, and its multidrug resistant variant (MDR-MCF-7) cultured as spheroids or as monolayers. Three-dimensional...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: dit Faute MA,Laurent L,Ploton D,Poupon MF,Jardillier JC,Bobichon H

    更新日期:2002-01-01 00:00:00

  • Multiple pathways of cell invasion are regulated by multiple families of serine proteases.

    abstract::The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that co...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Del Rosso M,Fibbi G,Pucci M,D'Alessio S,Del Rosso A,Magnelli L,Chiarugi V

    更新日期:2002-01-01 00:00:00

  • Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model.

    abstract::Metastasis is the most devastating aspect of cancer and it is the main cause of morbidity and mortality in cancer patients. Tumor cell adhesion to the vascular endothelial cell lining is an important step in metastatic progression and is prompted by platelets. Mucin 1 is over-expressed and aberrantly glycosylated in m...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Sudha T,Phillips P,Kanaan C,Linhardt RJ,Borsig L,Mousa SA

    更新日期:2012-06-01 00:00:00

  • Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver.

    abstract::This article discusses the role of carcinoembryonic antigen (CEA) as a facilitator of the inflammatory response and its effect on colorectal cancer hepatic metastasis. Colorectal cancer accounts for 11% of all cancers in the United States and the majority of deaths are associated with liver metastasis. If left untreat...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Thomas P,Forse RA,Bajenova O

    更新日期:2011-12-01 00:00:00

  • Mapping protein signal pathway interaction in sarcoma bone metastasis: linkage between rank, metalloproteinases turnover and growth factor signaling pathways.

    abstract::We applied reverse phase protein microarrays technology to map signal pathway interactions in a discovery set of 34 soft tissue sarcoma (STS) bone metastases compared to healthy bone. Proteins associated with matrix remodeling (MMP), adhesion (FAK Y576/577, Syndecan-1), and growth/survival (IGF1R Y1135/1136, PI3K, EGF...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Conti A,Espina V,Chiechi A,Magagnoli G,Novello C,Pazzaglia L,Quattrini I,Picci P,Liotta LA,Benassi MS

    更新日期:2014-01-01 00:00:00

  • Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases.

    abstract::To analyze the prognostic value of the extent of peritumoral brain edema in patients operated for single brain metastases (BM), we retrospectively evaluated pre-operative magnetic resonance images in a discovery cohort of 129 patients and a validation cohort of 118 patients, who underwent neurosurgical resection of a ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Spanberger T,Berghoff AS,Dinhof C,Ilhan-Mutlu A,Magerle M,Hutterer M,Pichler J,Wöhrer A,Hackl M,Widhalm G,Hainfellner JA,Dieckmann K,Marosi C,Birner P,Prayer D,Preusser M

    更新日期:2013-04-01 00:00:00

  • Tamoxifen resistance in breast cancer cells is accompanied by an enhanced motile and invasive phenotype: inhibition by gefitinib ('Iressa', ZD1839).

    abstract::Despite an initial response to antihormonal therapies, the development of resistance will occur in a significant number of breast cancer patients. The mechanisms that underlie acquired resistance are not yet clear. Using a previously established in vitro cell model of tamoxifen resistance in MCF7 cells, shown to displ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Hiscox S,Morgan L,Barrow D,Dutkowskil C,Wakeling A,Nicholson RI

    更新日期:2004-01-01 00:00:00

  • SCUBE3 regulation of early lung cancer angiogenesis and metastatic progression.

    abstract::Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is strongly expressed in extremely invasive lung carcinoma. We showed in our previous study that SCUBE3 triggers the transforming growth factor-β pathway and subsequently promotes tumor angiogenesis and the epithelial-mesenchymal transition (EMT). Howeve...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Chou CH,Cheng YF,Siow TY,Kumar A,Peck K,Chang C

    更新日期:2013-08-01 00:00:00