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 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.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Suarez-Cuervo C,Merrell MA,Watson L,Harris KW,Rosenthal EL,Väänänen HK,Selander KSdoi
10.1007/s10585-004-3503-xsubject
Has Abstractpub_date
2004-01-01 00:00:00pages
525-33issue
6eissn
0262-0898issn
1573-7276journal_volume
21pub_type
杂志文章abstract：:Development of central nervous system (CNS) metastases in breast cancer (BC) is associated with poor prognosis. The incidence of CNS metastases in metastatic BC is reported to be about 10-16 %, but different subtypes of BC are associated with different risk of developing CNS metastases. We retrospectively analysed the...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-013-9594-5
更新日期：2013-12-01 00:00:00
abstract：:We investigated the role of signal transduction systems in the attachment of human uveal melanoma cells to matrix proteins. Ocular melanoma cells established from primary tumours attached rapidly to all substrates examined. Preferred substrates of attachment were collagens type I, III and IV and fibronectin rather tha...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF01755881
更新日期：1994-11-01 00:00:00
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
doi：10.1007/s10585-010-9322-3
更新日期：2010-04-01 00:00:00
abstract：:Fischer 344/CRJ rats harbor a G633R substitution in dipeptidyl peptidase IV (DPP IV) that leads to retention and degradation of the mutant protein in the endoplasmic reticulum (Tsuji E, Misumi Y, Fujiwara T et al. Biochemistry 1992; 31 (47): 11921-7). However, when these rats were used as a 'protein knock-out' model i...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1006757525190
更新日期：1999-01-01 00:00:00
abstract：:Metastasis is a vital target for cancer treatment, since the majority of cancer patients die from metastatic, rather than the primary disease. KiSS1 has been identified as a metastasis suppressor gene in melanoma and breast carcinomas. We show here that KiSS1 is also a metastasis suppressor in human ovarian cancer. Ov...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-005-8186-4
更新日期：2005-01-01 00:00:00
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
doi：10.1023/a:1006639804430
更新日期：1999-05-01 00:00:00
abstract：:Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin or BM-40) is a glycoprotein component of the extracellular matrix that has been reported to be involved with a variety of cellular processes. Although SPARC expression levels are frequently altered in a variety of tumor types, the exact im...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-007-9126-2
更新日期：2008-01-01 00:00:00
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
doi：10.1007/BF00123395
更新日期：1996-09-01 00:00:00
abstract：:A murine mammary carcinoma, which had a high potential for metastasis to the lungs, was established in culture, and from the parent line several clonally derived variants were isolated, showing different characteristics including metastatic potential. C1, a high metastatic clone, and C2, a low one, were selected for f...
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
abstract：:Immunotherapy by vaccination represents a novel method for treatment of cancer. In this regard, vaccines with the broadest possible menu of relevant antigens stand the greatest chance of success. Tissue vaccines are composed of material harvested directly from tumors and contain not only antigens associated with neopl...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-008-9213-z
更新日期：2008-01-01 00:00:00
abstract：:Breast cancer has a predilection for metastasis to the bone marrow. The preprotachykinin-I (PPT-I) gene has a central role in the early migration of breast cancer cells into the bone marrow, making this organ a latent repository of the cancer cells. This study investigated whether the invasive and metastatic potential...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-006-9001-6
更新日期：2005-01-01 00:00:00
abstract：:Brain metastases present a significant public health issue, affecting more than 100,000 patients per year in the U.S. and result in significant morbidity. Brain metastases can occur in a variety of clinical situations ranging from multiple brain metastases with uncontrolled systemic disease to a solitary metastasis in...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章,评审
doi：10.1007/s10585-017-9860-z
更新日期：2017-10-01 00:00:00
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
doi：10.1007/s10585-014-9658-1
更新日期：2014-08-01 00:00:00
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
doi：10.1007/s10585-006-9034-x
更新日期：2006-01-01 00:00:00
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
doi：10.1023/a:1006540824969
更新日期：1998-04-01 00:00:00
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
doi：10.1007/s10585-021-10074-2
更新日期：2021-01-24 00:00:00
abstract：:We have established two highly metastatic tumor clones, D-1 and F-3, which have the distinct features of undergoing pulmonary metastases. Both clones were derived from a skin squamous cell carcinoma (SqC-NH), which had spontaneously occurred in DS-Nh mice. F-3 was morphologically spindle-shaped in tumor mass and adher...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF00058055
更新日期：1993-07-01 00:00:00
abstract：:We have investigated the gelatinase profiles and invasiveness of clonal tumour sublines derived from a spontaneously arising mammary tumour in a Balb/cfC3H mouse. The 67NR. 66c14 and 4T1.2 sublines have low, intermediate and high metastatic potential respectively. In Boyden chamber studies, Matrigel invasion was seen ...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1011953118186
更新日期：2000-01-01 00:00:00
abstract：:The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin-enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal adenocarcinomas were investigated in male Wistar rats. From the beginning of the study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1025883129932
更新日期：2003-01-01 00:00:00
abstract：:Tumour endothelial markers (TEMs) are a newly discovered family of endothelial markers associated with tumour specific angiogenesis. This study sought to examine the levels of expression for TEMs in human breast cancer. Breast cancer tissues (n = 120) together with normal background tissues (n = 33) were obtained afte...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/b:clin.0000017168.83616.d0
更新日期：2004-01-01 00:00:00
abstract：:The occurrence of metastases is the hallmark of cancer. Development of metastasis severely affects prognosis and survival. It limits or discourages therapeutic interventions since no therapies are available to block or prevent cancer invasion. In order to invade, epithelial cancer cells need to penetrate through the b...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章,评审
doi：10.1023/a:1011879900554
更新日期：2000-01-01 00:00:00
abstract：:A new model for the study of spontaneous bone metastasis has been developed which allows for the quantification of metastatic tumor burden and cancer cell growth rate, and which describes the progressive changes in bone morphology. Walker 256 (W256) cells or vehicle were injected into the left upper thigh muscle of ma...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF00133469
更新日期：1992-11-01 00:00:00
abstract：:Recent studies have indicated that KHT fibrosarcoma or B16 melanoma cell variants capable of forming experimental metastases in the lungs of mice after i.v. injection are created stochastically at high rates (approximately 10(-5)/cell/generation). Expression of this phenotype is unstable and hence expanding population...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF00117930
更新日期：1986-07-01 00:00:00
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
doi：10.1007/s10585-004-2696-3
更新日期：2004-01-01 00:00:00
abstract：:The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (% kcal.) for 7 weeks before they were subcutaneously injected with 2.5 × 10⁵ viable carcinoma cells. The primary tumor was resec...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/s10585-010-9347-7
更新日期：2010-12-01 00:00:00
abstract：:Although the loss of sulfomucins was known as an indicator of carcinogenesis and malignant progression of colonic epithelia, it was not known whether the loss was directly related to the malignant behavior of colon carcinoma cells. We have studied the biological properties of LS174T human colon carcinoma cells before ...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1006654027742
更新日期：1999-03-01 00:00:00
abstract：:It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and ...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章,评审
doi：10.1007/s10585-018-9903-0
更新日期：2018-04-01 00:00:00
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
doi：10.1007/s10585-018-9944-4
更新日期：2018-12-01 00:00:00
abstract：:Integrins expressed on endothelial cells modulate cell migration and survival during angiogenesis. Integrins expressed on carcinoma cells potentiate metastasis by facilitating invasion and movement across blood vessels. We describe the activities of two synthetic low-molecular-weight peptidomimetics of the ligand amin...
journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/b:clin.0000024764.93092.5f
更新日期：2004-01-01 00:00:00
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
doi：10.1023/a:1006542301794
更新日期：1998-08-01 00:00:00
