MTBP inhibits migration and metastasis of hepatocellular carcinoma.


:Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding Protein (MTBP) has been implicated in the suppression of cell migration and cancer metastasis. However, clinical significance of MTBP, particularly in human cancer, is poorly understood. Specifically, clinical relevance of MTBP in human HCC has never been investigated. Here we demonstrated that expression of MTBP was significantly reduced in human HCC tissues compared to adjacent non-tumor tissues. MTBP expression was negatively correlated with capsular/vascular invasion and lymph node metastasis. Overexpression of MTBP resulted in the suppression of the migratory and metastatic potential of HCC cells, while its downregulation increased the migration. Consistent with the previous report, MTBP endogenously bound to alpha-actinin 4 (ACTN4) and suppressed ACTN4-mediated cell migration in multiple HCC cell lines. However, MTBP also inhibited migratory potential of PLC/PRF/5 HCC cells whose migration was not altered by manipulation of ACTN4 expression. These results suggest that mechanisms behind MTBP-mediated migration suppression may not be limited to the pathway involving ACTN4 in certain cellular contexts. Additionally, as a potential mechanism for reduced MTBP expression in tumors, we found that MTBP expression was increased following the treatment with histone deacetylase inhibitors (HDIs). Our study, for the first time, provides clinical relevance of MTBP in the suppression of HCC metastasis.


Clin Exp Metastasis


Bi Q,Ranjan A,Fan R,Agarwal N,Welch DR,Weinman SA,Ding J,Iwakuma T




Has Abstract


2015-04-01 00:00:00












  • Time to metastatic relapse and breast cancer cells dissemination in bone marrow at metastatic relapse.

    abstract::Breast cancer dissemination can be monitored in patients by detecting circulating and/or disseminated tumor cells. However, bone marrow disseminated tumor cells (BM DTC) may undergo a dormancy during several years before growing (or not) into clinically detectable metastases. We therefore hypothesized that breast canc...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bidard FC,Vincent-Salomon A,Sigal-Zafrani B,Rodrigues M,Diéras V,Mignot L,Sastre-Garau X,Poupon MF,Pierga JY

    更新日期:2008-01-01 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

  • Metrazol enhances brain penetration and therapeutic efficacy of some anticancer agents: implications for brain metastases.

    abstract::The concurrent administration of Metrazol (60 mg/kg, i.v.) to anaesthetized rats enhances the cerebral penetration of the anticancer agent razoxane. Such an enhancement leads to an increase in the therapeutic efficacy of razoxane against intracerebrally sequestered L1210 leukaemia cells in mice. The combination of Met...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Greig N,Newell D,Hellmann K

    更新日期:1984-01-01 00:00:00

  • Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator.

    abstract::Type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP9 are implicated in tumor invasion and metastasis. In patients with nasopharyngeal carcinoma (NPC), poor prognosis due to development of local and distant metastasis has been reported to be predicted by antibody titers against the Z protein which is an AP-1...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Yoshizaki T,Sato H,Murono S,Pagano JS,Furukawa M

    更新日期:1999-07-01 00:00:00

  • Association of SIBA treatment and a Met-depleted diet inhibits in vitro growth and in vivo metastatic spread of experimental tumor cell lines.

    abstract::We have used 5'-deoxy-5'-S isobutyl-thioadenosine (SIBA), an analog of S-adenosylhomocysteine, alone or in association with a methionine-depleted diet in order to obtain an antitumoral effect in two different tumor models: a transplantable rat rhabdomyosarcoma (RMS-J1) induced by i.m. injection of nickel and the well-...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Breillout F,Poupon MF,Blanchard P,Lascaux V,Echinard-Garin P,Robert-Gero M

    更新日期:1988-01-01 00:00:00

  • Salvage treatment for recurrences after first resection of colorectal liver metastases: the impact of histopathological growth patterns.

    abstract::The majority of patients recur after resection of colorectal liver metastases (CRLM). Patients with CRLM displaying a desmoplastic histopathological growth pattern (dHGP) have a better prognosis and lower probability of recurrence than patients with non-dHGP CRLM. The current study evaluates the impact of HGP type on ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Nierop PMH,Galjart B,Höppener DJ,van der Stok EP,Coebergh van den Braak RRJ,Vermeulen PB,Grünhagen DJ,Verhoef C

    更新日期:2019-04-01 00:00:00

  • Analysis of c-fos, c-jun, c-erbB1, c-erbB2 and c-myc in primary lung carcinomas and their lymph node metastases.

    abstract::The purpose of this study was to identify possible alterations in proto-oncogenes (c-fos, c-jun, c-erbB1, c-erbB2 and c-myc) at the protein level in primary lung carcinomas and simultaneous metastatic lymph nodes of 21 patients. The analysis showed that proteins of c-jun and c-myc were expressed in a significantly hig...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Volm M,van Kaick G,Mattern J

    更新日期:1994-07-01 00:00:00

  • CD44 expression and hyaluronic acid binding of malignant glioma cells.

    abstract::The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigat...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Knüpfer MM,Poppenborg H,Hotfilder M,Kühnel K,Wolff JE,Domula M

    更新日期:1999-02-01 00:00:00

  • Ras suppressor-1 promotes apoptosis in breast cancer cells by inhibiting PINCH-1 and activating p53-upregulated-modulator of apoptosis (PUMA); verification from metastatic breast cancer human samples.

    abstract::Metastasis, responsible for most deaths from breast cancer (BC), is a multistep process leading to cancer cell spread. Extracellular matrix (ECM)-related adhesion and apoptosis resistance play pivotal role in metastasis. Ras suppressor-1 (RSU-1) localizes to cell-ECM adhesions and binds to pro-survival adhesion protei...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Giotopoulou N,Valiakou V,Papanikolaou V,Dubos S,Athanassiou E,Tsezou A,Zacharia LC,Gkretsi V

    更新日期:2015-03-01 00:00:00

  • Over-expression of human CD44s in murine 3T3 cells: selection against during primary tumorigenesis and selection for during micrometastasis.

    abstract::Human CD44 standard isoform (hCD44s) cDNA regulated by a high-expressing promoter was transfected into Balb/c 3T3 cells and the tumorigenic and metastatic capacities of the transfectants were investigated in nude mice at the subcutaneous site. One of three transfectants was tumorigenic. hCD44s expression was lost in t...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kogerman P,Sy MS,Culp LA

    更新日期:1998-01-01 00:00:00

  • IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.

    abstract::The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of I...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Herzberg F,Schöning M,Schirner M,Topp M,Thiel E,Kreuser ED

    更新日期:1996-03-01 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

  • 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

  • Breast cancer cells with inhibition of p38alpha have decreased MMP-9 activity and exhibit decreased bone metastasis in mice.

    abstract::p38 belongs to a family of mitogen-activated protein kinases, which transfer extracellular signals into intracellular responses. p38 is also frequently detected in clinical breast cancer specimens, but its role as a prognostic factor is not known. Of the various p38 isoforms, p38alpha has been shown to mediate the in ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Suarez-Cuervo C,Merrell MA,Watson L,Harris KW,Rosenthal EL,Väänänen HK,Selander KS

    更新日期:2004-01-01 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

  • Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions.

    abstract::The interaction between circulating tumor cells and blood components, mainly platelets, plays an important role during metastasis. In this study, we prepared liposomes containing the platelet aggregation inhibitor Cilostazol (Cil-L). The objective of this study was to investigate the effect of this Cil-L on platelet a...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Wenzel J,Zeisig R,Fichtner I

    更新日期:2010-01-01 00:00:00

  • Resistance of the embryonic notochord to invasion by malignant neurogenic tumor cells in vitro.

    abstract::Very few tissues in vivo are resistant to invasion by malignant cells. In this paper, confrontation cultures consisting of chick embryonic notochord fragments and cell aggregates from three malignant neurogenic cell lines showed a resistance of the embryonic organ to malignant invasion by tumor cells. The mechanism of...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Schroyens W,Camon J,De Ridder L

    更新日期:1991-07-01 00:00:00

  • Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts.

    abstract::Blood samples, bone marrow, tumours and metastases where possible were collected from SCID mice bearing orthotopic xenografts of the triple-negative MDA-MB-468 cell line or a transplantable ER-positive patient derived xenograft (ED-03), and assessed using human-specific, tandem-nested RT-qPCR for markers relating to d...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Tachtsidis A,Le AV,Blick T,Gunasinghe D,De Sousa E,Waltham M,Dobrovic A,Thompson EW

    更新日期:2019-08-01 00:00:00

  • Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) in melanoma.

    abstract::This short review offers an update on the first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) for patients with melanoma, and briefly traces the development of intraoperative lymphatic mapping and sentinel node biopsy. ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,多中心研究,评审


    authors: Morton DL

    更新日期:2012-10-01 00:00:00

  • Involvement of cell-cell adhesion molecules in liver colonization by metastatic murine lymphoma/lymphosarcoma variants.

    abstract::Metastatic variant sublines of the murine RAW117 large cell lymphoma or lymphosarcoma have been established in vitro by sequential cycles of harvesting of liver tumor nodules after intravenous inoculation of tumor cell suspensions into syngeneic BALB/c mice. After five and ten in vivo selections for liver colonization...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: McGuire EJ,Mascali JJ,Grady SR,Nicolson GL

    更新日期:1984-07-01 00:00:00

  • Lymphatic metastasis in breast cancer: importance and new insights into cellular and molecular mechanisms.

    abstract::Lymph node metastasis is the main prognosis factor in a number of malignancies, including breast carcinomas. The means by which lymph node metastases arise is not fully understood, and many questions remain about their importance in the further spread of breast cancer. Nevertheless, a number of key cellular and molecu...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Eccles S,Paon L,Sleeman J

    更新日期:2007-01-01 00:00:00

  • A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful?

    abstract::Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor with a key role in many physiological and pathological processes. Investigation into the implications of circulating levels of this cytokine is progressing at an exponential rate. However, there are important inconsistencies between reports...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Hormbrey E,Gillespie P,Turner K,Han C,Roberts A,McGrouther D,Harris AL

    更新日期:2002-01-01 00:00:00

  • Stimulation of tumor cell growth in vitro by a monoclonal antibody to a tumor specific protein (TSP-180) present on the cell surface of 3LL cells.

    abstract::Proliferation capacity and MHC class I antigen expression of two Lewis lung carcinoma (3LL) metastatic variants (C87, BC215) grown under defined experimental conditions (serum-free defined medium or 10 per cent serum) have been studied following exposure to MoAb 135-13C which recognizes on these cells a tumor surface ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Sacchi A,Piaggio G,Rizzo MA,Falcioni R,Kennel SJ

    更新日期:1989-01-01 00:00:00

  • Is adjuvant treatment with vinblastine effective in reducing the occurrence of distant metastasis in limited squamous cell lung cancer? A randomized study.

    abstract::In order to study the usefulness of treatment with vinblastine (VLB) in the prevention of cancer metastasis in squamous cell lung cancer, 50 patients with locoregional disease were randomized to receive either locoregional RT alone (group A) or a weekly intravenous bolus injection of VLB (6 mg/m2) concurrently with an...

    journal_title:Clinical & experimental metastasis

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Schallier DC,De Neve WJ,De Greve JL,Van Belle SP,De Wasch GJ,Dotremont G,Storme GA

    更新日期:1988-01-01 00:00:00

  • Characterization of thrombospondin synthesis, secretion and cell surface expression by human tumor cells.

    abstract::Previous studies have shown that thrombospondin (TSP) is an adhesion factor for some human tumor cells. The previous studies have shown further that tumor cells which utilize TSP as an adhesion factor also synthesize it. This study continues the effort to understand how TSP production and expression are regulated in h...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Varani J,Riser BL,Hughes LA,Carey TE,Fligiel SE,Dixit VM

    更新日期:1989-05-01 00:00:00

  • Cyclooxygenase-2 expression correlates with uPAR levels and is responsible for poor prognosis of colorectal cancer.

    abstract::Considering recent findings that cyclooxygensase-2 (COX-2) is involved in the progression of colorectal carcinoma (CRC), the role of COX-2 in promoting invasion and angiogenesis was investigated by evaluating the relationship of COX-2 expression to various clinicopathological variables, including plasminogen activatin...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Konno H,Baba M,Shoji T,Ohta M,Suzuki S,Nakamura S

    更新日期:2002-01-01 00:00:00

  • Effects of gamma irradiation on cultured rat and mouse microvessel endothelial cells: metastatic tumor cell adhesion, subendothelial matrix degradation, and secretion of tumor cell growth factors.

    abstract::The effects of gamma-irradiation on the properties of microvessel endothelial cells were studied in vitro. After incubating confluent endothelial cell monolayers in low serum-containing medium for 24 h, the monolayers were irradiated with 137Cs. Survival of rat lung microvessel endothelial (RLE) and mouse brain microv...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Nicolson GL,Custead SE,Dulski KM,Milas L

    更新日期:1991-09-01 00:00:00

  • Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens.

    abstract::We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small di...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Dolo V,Adobati E,Canevari S,Picone MA,Vittorelli ML

    更新日期:1995-07-01 00:00:00

  • The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remain...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Brind'Amour A,Webb M,Parapini M,Sidéris L,Segedi M,Chung SW,Chartier-Plante S,Dubé P,Scudamore CH,Kim PTW

    更新日期:2021-01-24 00:00:00

  • The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines.

    abstract::A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Cooper CR,Bhatia JK,Muenchen HJ,McLean L,Hayasaka S,Taylor J,Poncza PJ,Pienta KJ

    更新日期:2002-01-01 00:00:00