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


: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 vitro invasiveness of breast cancer cells through up-regulation of urokinase plasminogen activator (uPA). We studied the role of p38alpha in breast cancer bone metastases, using dominant negative blockade approach. Human MDA-MB-231 breast cancer clones stably expressing dominant negative p38alpha (p38/AF) exhibited decreased basal MMP-9 activity. TGF-beta1-induced MMP-9 activity was also blunted in these clones, as compared with controls in which TGF-betal up-regulated MMP-9 activity. Consistent with these findings, SB202190, a specific p38 inhibitor, also inhibited TGF-beta1-induced MMP-9 activity in parental cells. The p38/AF clones exhibited also reduced uPA production after growth on vitronectin and decreased cell motility, as compared with controls. VEGF production levels in all the studied clones were similar. The p38/AF clone, which had similar in vitro growth rate as the control pcDNA3 clone, formed significantly less bone metastases in a mouse model, as compared with the control clone. In conclusion, inhibition of the p38alpha pathway results in decreased MMP-9 activity, impaired uPA expression and decreased motility, all of which may contribute to the decreased formation of bone metastasis.


Clin Exp Metastasis


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




Has Abstract


2004-01-01 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

  • Astrocyte-induced Reelin expression drives proliferation of Her2+ breast cancer metastases.

    abstract::Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Jandial R,Choy C,Levy DM,Chen MY,Ansari KI

    更新日期:2017-02-01 00:00:00

  • The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma.

    abstract::High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to cont...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Cipollone JA,Graves ML,Köbel M,Kalloger SE,Poon T,Gilks CB,McNagny KM,Roskelley CD

    更新日期:2012-03-01 00:00:00

  • Thymosin beta15 expression in tumor cell lines with varying metastatic potential.

    abstract::We previously isolated thymosin beta15 from highly metastatic Dunning rat prostatic carcinoma cells. Immunohistochemical study of human prostate cancer specimens revealed a general correlation between Gleason grade and thymosin beta15 expression, with high-grade (more malignant) tumors showing increased staining compa...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bao L,Loda M,Zetter BR

    更新日期:1998-04-01 00:00:00

  • Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7.

    abstract::The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesi...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Meincke M,Tiwari S,Hattermann K,Kalthoff H,Mentlein R

    更新日期:2011-12-01 00:00:00

  • Experimental liver metastasis: standards for local cell implantation to study isolated tumor growth in mice.

    abstract::Experimental hepatic metastasis of colorectal tumors is frequently studied by local intrahepatic tumor cell implantation. However, although a variety of factors of the implantation procedure may markedly influence tumor growth characteristics, standards are not defined yet. Herein, we studied the effect of different m...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kollmar O,Schilling MK,Menger MD

    更新日期:2004-01-01 00:00:00

  • Enhanced cell surface CD44 variant (v6, v9) expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration: novel post-transcriptional, post-translational regulation.

    abstract::Osteopontin (OPN) is a glycosylated, secreted phosphoprotein that functions both as a cell attachment and chemotactic factor. Elevated expression of OPN confers enhanced metastatic ability on transformed cells, suggesting that OPN may contribute to the malignant progression of tumors. Migration of mammary carcinoma ce...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Khan SA,Cook AC,Kappil M,Günthert U,Chambers AF,Tuck AB,Denhardt DT

    更新日期:2005-01-01 00:00:00

  • Predictors of prognosis of synchronous brain metastases in small-cell lung cancer patients.

    abstract::Patients with small cell lung cancer (SCLC) are more likely to have synchronous brain metastasis (SBM) at the time of diagnosis than patients with any other extracranial primary malignancy. We sought to identify which factors predicted an increased risk of SBM in SCLC as well as which factors affected the prognosis of...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Reddy SP,Dowell JE,Pan E

    更新日期:2020-08-01 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

    更新日期:2015-10-01 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

  • The lack of correlation between experimental metastatic potential and platelet aggregating activity of B16 melanoma clones viewed in relation to tumor cell heterogeneity.

    abstract::Two widely used B16 melanoma cell lines of low and high lung colonizing potential (B16-F1 and B16-F10) were compared in their ability to induce platelet aggregation. The results of these experiments showed a reproducible difference in platelet aggregating activity of these two cell lines which directly correlated with...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kimura AK,Mehta P,Xiang JH,Lawson D,Dugger D,Kao KJ,Lee-Ambrose L

    更新日期:1987-04-01 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

  • 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

  • Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins.

    abstract::At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence. The presence of ascites, which acts as a dynamic reservoir of active molecules and cellular components, correlates with the OC peritoneal metastasis and is associated with poor pro...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Carduner L,Leroy-Dudal J,Picot CR,Gallet O,Carreiras F,Kellouche S

    更新日期:2014-08-01 00:00:00

  • High-dose ionizing radiation-induced hematotoxicity and metastasis in mice model.

    abstract::Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been i...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Shin JW,Son JY,Raghavendran HR,Chung WK,Kim HG,Park HJ,Jang SS,Son CG

    更新日期:2011-12-01 00:00:00

  • Differential growth and responsiveness to cancer therapy of tumor cells in different environments.

    abstract::Tumor metastasis often confers poor prognosis for cancer patients due to lack of comprehensive strategy in dealing with cells growing in different environment. Current anticancer therapies have incomplete effectiveness because they were designed assuming metastatic tumors behave similarly in different organs. We hypot...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Alsaggar M,Yao Q,Cai H,Liu D

    更新日期:2016-02-01 00:00:00

  • Inhibition of protein synthesis, pulmonary localization and pulmonary tumour formation by drug-treated tumour cells as a means of predicting their chemosensitivity.

    abstract::Mouse mammary carcinoma cells were exposed in vitro to increasing concentrations of doxorubicin hydrochloride [adriamycin (ADR)] or 5-fluorouracil (5-FU). Uptake of [75Se]selenomethionine (75SeM) in a methionine-deficient medium measured the resulting inhibition of protein synthesis by the tumour cells. This was compa...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Lai T,Stonebridge BR,Black J,Symes MO

    更新日期:1989-07-01 00:00:00

  • Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas.

    abstract::This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, M...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Akimoto T,Kawabe S,Grothey A,Milas L

    更新日期:1999-03-01 00:00:00

  • GPR56 plays varying roles in endogenous cancer progression.

    abstract::GPR56, a non-classical adhesion receptor, was previously reported to suppress tumor growth and metastasis in xenograft models using human melanoma cell lines. To understand whether GPR56 plays similar roles in the development of endogenous tumors, we analyzed cancer progression in Gpr56 (-/-) mice using a variety of t...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Xu L,Begum S,Barry M,Crowley D,Yang L,Bronson RT,Hynes RO

    更新日期:2010-04-01 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

  • Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231 human breast cancer cells.

    abstract::We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231 human breast cancer cells involves both transcriptional and post-transcriptional mechanisms, and that the continuous presence of ConA is required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995). In an ef...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Yu M,Sato H,Seiki M,Spiegel S,Thompson EW

    更新日期:1998-02-01 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

  • A novel in vitro assay system for transendothelial tumor cell invasion: significance of E-selectin and alpha 3 integrin in the transendothelial invasion by HT1080 fibrosarcoma cells.

    abstract::The interaction of tumor cells with endothelial cells is a key event in tumor metastasis. We established an in vitro invasion assay system, in which the invasion of tumor cells after interaction with endothelial cells can be examined. Two chamber culture wells separated by porous membrane were used. Human umbilical ve...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Okada T,Okuno H,Mitsui Y

    更新日期:1994-07-01 00:00:00

  • Functional blocking of specific integrins inhibit colonic cancer migration.

    abstract::For more effective oncological management of disseminated colorectal cancer, therapies must be devised that target the different individual stages of metastasis development. Recent work showed that integrin subunits alpha2, alpha6 and beta4 are involved in the colorectal cancer cell extravasation process. By means of ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Robertson JH,Yang SY,Winslet MC,Seifalian AM

    更新日期:2009-01-01 00:00:00

  • Site-dependence of invasiveness of ECA109 human oesophageal carcinoma cells in nude mice.

    abstract::ECA109 human oesophageal carcinoma cells were injected either subcutaneously or intraperitoneally into BALB/CATc 1-nu/nu mice. After 23 weeks tumours were examined histologically and by scanning electron microscopy. Subcutaneous ECA109 tumours were well-delineated without signs of invasion. By contrast, intra-abdomina...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Gao J,Xue KX,Li BG,Dong HY,Wei LS,Zhang ZH,Tian S,Xu ZG

    更新日期:1984-07-01 00:00:00

  • Nitric oxide induced by tumor cells activates tumor cell adhesion to endothelial cells and permeability of the endothelium in vitro.

    abstract::Human fibrosarcoma HT1080 cell surface phenotype analysis revealed the expression of "cluster of differentiation 15" (CD15) antigen and to a lesser extent, of "very late antigen-4" (VLA-4). Expression of "endothelial-leukocyte adhesion molecule-1" (ELAM-1) was negligible on resting human umbilical vascular endothelial...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Yudoh K,Matsui H,Tsuji H

    更新日期:1997-11-01 00:00:00

  • 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

  • Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer.

    abstract::Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer known. IBC carries a guarded prognosis primarily due to rapid onset of disease, typically within six months, and the propensity of tumor emboli to invade the dermal lymphatics and spread systemically. Although the clinical manif...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: van Golen KL,Bao LW,Pan Q,Miller FR,Wu ZF,Merajver SD

    更新日期:2002-01-01 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

  • Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature.

    abstract::Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: PosthumaDeBoer J,Witlox MA,Kaspers GJ,van Royen BJ

    更新日期:2011-06-01 00:00:00