TIMP-3 deficiency in the host, but not in the tumor, enhances tumor growth and angiogenesis.

Abstract:

:Tumor cells, stromal cell compartment and the extracellular matrix (ECM) together generate a multifaceted tumor microenvironment. Matrix metalloproteinases and their tissue inhibitors (TIMPs) provide a means for tumor-stromal interaction during tumorigenesis. Among TIMPs, TIMP-3 is uniquely localized to the ECM and is frequently silenced in human cancers. Here, we asked whether the absence of TIMP-3 in the tumor cell or the host affects the process of tumorigenesis. Timp-3(-/-) ES-cell clones were generated and used to develop teratomas in nude mice. Timp-3(-/-) teratomas showed similar tumor take, growth, and angiogenesis compared to timp-3(+/+) teratomas. To study the effect of TIMP-3 ablation in the host stroma, we measured the growth kinetics of subcutaneous B16F10 melanomas in timp-3(-/-) and wild-type littermates. Tumors grew significantly faster in timp-3(-/-) than in wild-type mice and their CD31 content was significantly higher indicating increased angiogenesis. Augmented angiogenesis in timp-3(-/-) mice was directly tested using Matrigel plug and Gelfoam assays. In response to FGF-2, timp-3(-/-) endothelial cells invaded more efficiently, leading to enhanced formation of functional blood vessels. Thus, TIMP-3 deficiency in the host, but not in the tumor per se, leads to enhanced tumor growth and angiogenesis. TIMP-3 located within the tumor microenvironment inhibits tumorigenesis.

journal_name

Oncogene

journal_title

Oncogene

authors

Cruz-Muñoz W,Kim I,Khokha R

doi

10.1038/sj.onc.1209104

subject

Has Abstract

pub_date

2006-01-26 00:00:00

pages

650-5

issue

4

eissn

0950-9232

issn

1476-5594

pii

1209104

journal_volume

25

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Cell-penetrating H4 tail peptides potentiate p53-mediated transactivation via inhibition of G9a and HDAC1.

    abstract::Histone acetylation has a central role in establishing an active chromatin environment. The functional contribution of histone acetylation to chromatin transcription is accomplished by a dominant action of histone acetyltransferases over repressive histone-modifying activities at gene promoters; misregulation of these...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.273

    authors: Heo K,Kim JS,Kim K,Kim H,Choi J,Yang K,An W

    更新日期:2013-05-16 00:00:00

  • CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation.

    abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.340

    authors: Nie J,Liu L,Xing G,Zhang M,Wei R,Guo M,Li X,Xie P,Li L,He F,Han W,Zhang L

    更新日期:2014-07-10 00:00:00

  • Ets-related protein E1A-F can activate three different matrix metalloproteinase gene promoters.

    abstract::An Ets-related E1A-F has been characterized as an enhancer-binding protein for the adenovirus E1A gene. Here we show, in transient expression assays, that E1A-F can activate three different subclasses of the matrix metalloproteinase gene promoters. Expressions of the chloramphenicol acetyltransferase (CAT) reporter ge...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Higashino F,Yoshida K,Noumi T,Seiki M,Fujinaga K

    更新日期:1995-04-06 00:00:00

  • Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce miR-21 expression, PDCD4 downregulation and breast cancer metastasis.

    abstract::Membrane overexpression of the receptor tyrosine kinase ErbB-2 (MErbB-2) accounts for a clinically aggressive breast cancer (BC) subtype (ErbB-2-positive) with increased incidence of metastases. We and others demonstrated that nuclear ErbB-2 (NErbB-2) also plays a key role in BC and is a poor prognostic factor in ErbB...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.281

    authors: Venturutti L,Romero LV,Urtreger AJ,Chervo MF,Cordo Russo RI,Mercogliano MF,Inurrigarro G,Pereyra MG,Proietti CJ,Izzo F,Díaz Flaqué MC,Sundblad V,Roa JC,Guzmán P,Bal de Kier Joffé ED,Charreau EH,Schillaci R,Elizalde PV

    更新日期:2016-04-28 00:00:00

  • Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9 in 32Dcl3 cells.

    abstract::The MLL (HRX/ALL-1 gene is frequently disrupted in infantile leukemias and therapy-related leukemias and fused to various translocation partner genes. We previously showed that chimeric MLL proteins localize in the nuclei in a fashion similar to that of MLL protein even if the partner gene encodes a cytoplasmic protei...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202400

    authors: Joh T,Hosokawa Y,Suzuki R,Takahashi T,Seto M

    更新日期:1999-01-28 00:00:00

  • Oncogenic Ras increases sensitivity of colon cancer cells to 5-FU-induced apoptosis.

    abstract::Despite the fact that objective response rates to 5-FU are as low as 20%, 5-FU remains the most commonly used drug for the treatment of colorectal cancer. The lack of understanding of resistance to 5-FU, therefore, remains a significant impediment in maximizing its efficacy. We used intestinal epithelial cells with an...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208552

    authors: Klampfer L,Swaby LA,Huang J,Sasazuki T,Shirasawa S,Augenlicht L

    更新日期:2005-06-02 00:00:00

  • p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis.

    abstract::p8 is a stress-induced DNA-binding protein, biochemically related to the architectural chromatin binding HMG protein family and whose function is presently unknown. We obtained fibroblast from mice lacking p8 and found that p8 is involved in cell growth regulation and in apoptosis. p8(-/-) mouse embryonic fibroblasts ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205222

    authors: Vasseur S,Hoffmeister A,Garcia-Montero A,Mallo GV,Feil R,Kühbandner S,Dagorn JC,Iovanna JL

    更新日期:2002-03-07 00:00:00

  • Loss of Rassf1a enhances p53-mediated tumor predisposition and accelerates progression to aneuploidy.

    abstract::Loss of RASSF1A leads to several mitotic abnormalities, including cytokinesis failure and tetraploidization. Uncontrolled proliferation of tetraploid cells is known to trigger genomic instability and tumor development and is normally prevented through activation of a p53-dependent tetraploidy checkpoint. RASSF1A is th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.440

    authors: Tommasi S,Besaratinia A,Wilczynski SP,Pfeifer GP

    更新日期:2011-02-10 00:00:00

  • A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation.

    abstract::NUP98 has been involved in multiple recurrent chromosome rearrangements in leukemia. We identified a novel fusion between NUP98 and IQ motif containing G (IQCG) gene from a de novo acute T-lymphoid/myeloid leukemia harboring t(3;11)(q29q13;p15)del(3)(q29). IQCG has two putative coiled-coil domains and one IQ domain. T...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210999

    authors: Pan Q,Zhu YJ,Gu BW,Cai X,Bai XT,Yun HY,Zhu J,Chen B,Weng L,Chen Z,Xue YQ,Chen SJ

    更新日期:2008-05-29 00:00:00

  • TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells.

    abstract::Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be el...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.5

    authors: Bartucci M,Dattilo R,Moriconi C,Pagliuca A,Mottolese M,Federici G,Benedetto AD,Todaro M,Stassi G,Sperati F,Amabile MI,Pilozzi E,Patrizii M,Biffoni M,Maugeri-Saccà M,Piccolo S,De Maria R

    更新日期:2015-02-05 00:00:00

  • Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

    abstract::RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.489

    authors: Chen X,Makarewicz JM,Knauf JA,Johnson LK,Fagin JA

    更新日期:2014-11-20 00:00:00

  • GNAS(R201H) and Kras(G12D) cooperate to promote murine pancreatic tumorigenesis recapitulating human intraductal papillary mucinous neoplasm.

    abstract::Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that medi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.294

    authors: Taki K,Ohmuraya M,Tanji E,Komatsu H,Hashimoto D,Semba K,Araki K,Kawaguchi Y,Baba H,Furukawa T

    更新日期:2016-05-05 00:00:00

  • BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.

    abstract::High-grade gliomas (HGG) afflict both children and adults and respond poorly to current therapies. Epigenetic regulators have a role in gliomagenesis, but a broad, functional investigation of the impact and role of specific epigenetic targets has not been undertaken. Using a two-step, in vitro/in vivo epigenomic shRNA...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-1125-7

    authors: Green AL,DeSisto J,Flannery P,Lemma R,Knox A,Lemieux M,Sanford B,O'Rourke R,Ramkissoon S,Jones K,Perry J,Hui X,Moroze E,Balakrishnan I,O'Neill AF,Dunn K,DeRyckere D,Danis E,Safadi A,Gilani A,Hubbell-Engler B,Nus

    更新日期:2020-03-01 00:00:00

  • PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model.

    abstract::Transcriptional silencing of antitumor genes via CpG island methylation could be a mechanism mediating prostate cancer (PCa) progression from an androgen-sensitive (AS) to an androgen-insensitive (AI) state. We have used the methylation-sensitive restriction fingerprinting (MSRF) technique to identify novel CpG-rich s...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207076

    authors: Wu M,Ho SM

    更新日期:2004-01-08 00:00:00

  • Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells.

    abstract::A potential role for 1-oleoyl-sn-glycero-3-phosphate or lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in the regulation of malignant diseases has been widely considered. In this study, we found that in transformed astroglial cells, the expression profile of lysophospholipid receptor mRNA and the action...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208805

    authors: Malchinkhuu E,Sato K,Horiuchi Y,Mogi C,Ohwada S,Ishiuchi S,Saito N,Kurose H,Tomura H,Okajima F

    更新日期:2005-10-06 00:00:00

  • Analysis of chimeric Gag-Arg/Abl molecules indicates a distinct negative regulatory role for the Arg C-terminal domain.

    abstract::Arg and c-Abl represent the mammalian member of the Abelson family of nonreceptor protein tyrosine kinases. The two proteins are composed of SH2, SH3, kinase and C-terminal domains. To examine Arg structure-function relationships we analysed a Gag-Arg fusion protein, analogous to the oncogenic Gag-Abl fusion protein o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Mysliwiec T,Perego R,Kruh GD

    更新日期:1996-02-01 00:00:00

  • Development of cellular resistance to pp60v-src kinase-induced cell death.

    abstract::The v-src gene of Rous sarcoma virus (RSV) encodes pp60v-src, a tyrosine kinase that can initiate cellular transformation. High levels of v-src gene expression can either be cytotoxic or the cause of altered expression of cellular genes. Examination of cytotoxic thresholds is difficult because cells expressing high le...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Wu LW,Hackett PB

    更新日期:1995-10-19 00:00:00

  • The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription.

    abstract::BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206688

    authors: Cutress RI,Townsend PA,Sharp A,Maison A,Wood L,Lee R,Brimmell M,Mullee MA,Johnson PW,Royle GT,Bateman AC,Packham G

    更新日期:2003-08-07 00:00:00

  • V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors.

    abstract::The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.93

    authors: Nguyen-Lefebvre AT,Leprun G,Morin V,Viñuelas J,Couté Y,Madjar JJ,Gandrillon O,Gonin-Giraud S

    更新日期:2014-03-20 00:00:00

  • CHK2 stability is regulated by the E3 ubiquitin ligase SIAH2.

    abstract::The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis. Although CHK2 activation mechanisms have been amply described, very little is known...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.495

    authors: García-Limones C,Lara-Chica M,Jiménez-Jiménez C,Pérez M,Moreno P,Muñoz E,Calzado MA

    更新日期:2016-08-18 00:00:00

  • Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion.

    abstract::The regulation of cell adhesion and motility in human prostate is not well understood. We have previously shown that the endoglin gene is differently expressed during changes in prostate cell adhesion. Endoglin is a transmembrane transforming growth factor beta binding protein typically expressed by endothelial cells....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206117

    authors: Liu Y,Jovanovic B,Pins M,Lee C,Bergan RC

    更新日期:2002-11-28 00:00:00

  • Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues.

    abstract::Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209755

    authors: Hwang SI,Thumar J,Lundgren DH,Rezaul K,Mayya V,Wu L,Eng J,Wright ME,Han DK

    更新日期:2007-01-04 00:00:00

  • Inhibition of anchorage-independent growth and lung metastasis of A549 lung carcinoma cells by IkappaBbeta.

    abstract::To evaluate the role of the NF-kappaB signaling pathway in oncogenic transformation, we expressed IkappaBbeta, a specific inhibitor of NF-kappaB, in two human lung adenocarcinoma cell lines, A549 and H441. Expression of IkappaBbeta significantly reduced NF-kappaB activation induced by cotransfection with p65/RelA or T...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204293

    authors: Jiang Y,Cui L,Yie TA,Rom WN,Cheng H,Tchou-Wong KM

    更新日期:2001-04-26 00:00:00

  • Alterations in growth properties of human papilloma virus type 16 immortalised human cervical keratinocyte cell line correlate with amplification and overexpression of c-myc oncogene.

    abstract::Clinical and epidemiological data support a role for human papilloma virus (HPV) type 16 in the pathogenesis of cervical carcinoma. The W12 cell line contains HPV16 sequences, predominantly as a high copy number episome, and is immortalised in vitro, but non-tumourigenic. A morphologically distinct sub-line of the par...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Crook T,Greenfield I,Howard J,Stanley M

    更新日期:1990-04-01 00:00:00

  • Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21.3 region of homozygous loss in human tumours.

    abstract::Chromosomal deletions are a common feature of epithelial tumours and when further defined by homozygous deletions, are often the location of tumour suppressor genes. Deletions within the short arm of chromosome 3 occur very frequently in human carcinomas: a minimal region of loss at 3p21.3 (the Luca) region has been d...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205530

    authors: Smith AJ,Xian J,Richardson M,Johnstone KA,Rabbitts PH

    更新日期:2002-07-04 00:00:00

  • Recombinant Csk expressed in Escherichia coli is autophosphorylated on tyrosine residue(s).

    abstract::The C-terminal src kinase (Csk) is responsible for the phosphorylation of the carboxy-terminal tyrosine of several tyrosine kinases of the Src family. This phosphorylation site has a negative regulatory function. Csk is unique among the members of the protein tyrosine kinase family because it lacks the conserved tyros...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Bougeret C,Rothhut B,Jullien P,Fischer S,Benarous R

    更新日期:1993-05-01 00:00:00

  • Signal transduction pathways regulated by arsenate and arsenite.

    abstract::Arsenate and arsenite activate c-Jun N-terminal kinase (JNK), however, the mechanism by which this occurs is not known. By expressing inhibitory mutant small GTP-binding proteins, p21-activated kinase (PAK) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinases (MEKKs), we have ident...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203214

    authors: Porter AC,Fanger GR,Vaillancourt RR

    更新日期:1999-12-16 00:00:00

  • Intermediate filament dynamics and breast cancer: aberrant promoter methylation of the Synemin gene is associated with early tumor relapse.

    abstract::Synemin (SYNM) is a type IV intermediate filament that has recently been shown to interact with the LIM domain protein zyxin, thereby possibly modulating cell adhesion and cell motility. Owing to this multiplicity of potential functions relevant to cancer development, we initiated a study to decipher SYNM expression a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.229

    authors: Noetzel E,Rose M,Sevinc E,Hilgers RD,Hartmann A,Naami A,Knüchel R,Dahl E

    更新日期:2010-08-26 00:00:00

  • LMW-PTP is a positive regulator of tumor onset and growth.

    abstract::Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are an enzyme family that plays a key role in cell proliferation control by dephosphorylating/inactivating both tyrosine kinase receptors (such as PDGF, insulin, and ephrin receptors) and docking proteins (such, as beta-catenin) endowed with both adhesion a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207508

    authors: Chiarugi P,Taddei ML,Schiavone N,Papucci L,Giannoni E,Fiaschi T,Capaccioli S,Raugei G,Ramponi G

    更新日期:2004-05-13 00:00:00

  • Human oncogenes detected by a defined medium culture assay.

    abstract::Oncogenes in DNAs from human tumor cell lines have been detected by a new transformation assay. Cellular DNAs are transfected into NIH3T3 murine fibroblasts, and transformed cells are selected by maintaining cell cultures in a defined medium lacking platelet-derived or fibroblast growth factors. DNAs from eight of 17 ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Zhan X,Culpepper A,Reddy M,Loveless J,Goldfarb M

    更新日期:1987-01-01 00:00:00