Paracrine regulation of glioma cells invasion by astrocytes is mediated by glial-derived neurotrophic factor.


:It was suggested that the brain microenvironment plays a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion. In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined the downstream paracrine effect of glial-derived neurotrophic factor (GDNF) on tumor invasion. Astrocytes-conditioned media (ACM) significantly increased human and murine glioma cells migration compared to controls. This effect was inhibited when the activity of GDNF on glioma cells was blocked by RET-Fc chimera or anti-GDNF Ab and by small interfering RNA directed against GDNF expression by astrocytes. Glioma cells incubated with ACM led to time dependent phosphorylation of the GDNF receptor, RET and downstream activation of AKT. Tumor migration and GDNF-RET-AKT activation was inhibited by the RET small-molecule inhibitor pyrazolopyrimidine-1 (PP1) and by the AKT inhibitor LY294002. Finally, blocking of RET by PP1 or knockout of the RET coreceptor GFRα1 in glioma cells reduced the size of brain tumors in immunocompetent mice. We suggest a mechanism by which astrocytes attracted to the glioma tumors facilitate brain invasion by secretion of GDNF and activation of RET/GFRα1 receptors expressed by the cancer cells.


Int J Cancer


Shabtay-Orbach A,Amit M,Binenbaum Y,Na'ara S,Gil Z




Has Abstract


2015-09-01 00:00:00












  • Reproductive history and cancer of the biliary tract in women.

    abstract::Although reproductive factors have been shown to be related to the composition of bile and functioning of the biliary system, their relationship with biliary tract cancer has not been studied in detail. Between 1984 and 1987 we conducted a case-control study of 75 women with cancer of the biliary tract and 252 control...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Moerman CJ,Berns MP,Bueno de Mesquita HB,Runia S

    更新日期:1994-04-15 00:00:00

  • Recovery of leukocyte function after super-high-dose chemotherapy with peripheral blood stem cell transplantation in testicular cancer patients.

    abstract::Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSC...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Yamada Y,Hara I,Gohji K,Okada H,Arakawa S,Kamidono S

    更新日期:1997-07-03 00:00:00

  • Differences in the recognition of tumor-specific CD8+ T cells derived from solid tumor, metastatic lymph nodes and ascites in patients with gastric cancer.

    abstract::We established gastric cancer-specific CD8+ T-cell (T(CD8+)) lines derived from different lymphocyte sources in the same patients by repeated stimulation with mitomycin-C-treated autologous tumor cells with low-dose interleukin-2, and we compared recognition patterns among the T(CD8+) derived from solid tumor, lymph n...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kono K,Ichihara F,Iizuka H,Sekikawa T,Matsumoto Y

    更新日期:1997-06-11 00:00:00

  • Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.

    abstract::In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtaine...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究


    authors: Denny L,Adewole I,Anorlu R,Dreyer G,Moodley M,Smith T,Snyman L,Wiredu E,Molijn A,Quint W,Ramakrishnan G,Schmidt J

    更新日期:2014-03-15 00:00:00

  • Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T-cells in chronic lymphocytic leukemia.

    abstract::Antitumor immunity in chronic lymphocytic leukemia (CLL) is hampered by highly dysfunctional T-cells. Although certain T-cell subsets have been reported to be of prognostic significance in this disease, their interplay is complex and it remains incompletely understood which of these subsets significantly drive CLL pro...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Rissiek A,Schulze C,Bacher U,Schieferdecker A,Thiele B,Jacholkowski A,Flammiger A,Horn C,Haag F,Tiegs G,Zirlik K,Trepel M,Tolosa E,Binder M

    更新日期:2014-11-15 00:00:00

  • Chromosome-9 loss detected by fluorescence in situ hybridization in bladder cancer.

    abstract::A loss of chromosome-9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome-9 losses in bladder cancer, 125 formalin-fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe fo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sauter G,Moch H,Carroll P,Kerschmann R,Mihatsch MJ,Waldman FM

    更新日期:1995-04-21 00:00:00

  • A case-control study of diet and gastric cancer in northern Italy.

    abstract::Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for gastric cancer. D...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: La Vecchia C,Negri E,Decarli A,D'Avanzo B,Franceschi S

    更新日期:1987-10-15 00:00:00

  • Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways.

    abstract::A subgroup of head and neck squamous cell carcinomas (HNSCCs) contains high-risk human papillomavirus-type 16 (HPV16). The viral E6 and E7 oncoproteins inactivate the p53 and pRb proteins, respectively. We examined the causative effect of HPV16 E6 and E7 expression on the immortalization of normal oral keratinocytes (...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Smeets SJ,van der Plas M,Schaaij-Visser TB,van Veen EA,van Meerloo J,Braakhuis BJ,Steenbergen RD,Brakenhoff RH

    更新日期:2011-04-01 00:00:00

  • A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) status, age at diagnosis and cancer risk.

    abstract::Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumou...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Cederquist K,Golovleva I,Emanuelsson M,Stenling R,Grönberg H

    更新日期:2001-02-15 00:00:00

  • Transfection of the type I TGF-beta receptor restores TGF-beta responsiveness in pancreatic cancer.

    abstract::Transforming growth factor-beta (TGF-beta) signaling is initiated following heterodimerization of the type II TGF-beta receptor (TbetaRII) with the type I TGF-beta receptor (TbetaRI). Both receptors are required for TGF-beta responsiveness. In the present study, we characterized the actions of TGF-beta1 in T3M4 human ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wagner M,Kleeff J,Lopez ME,Bockman I,Massaqué J,Korc M

    更新日期:1998-10-05 00:00:00

  • Substrate-dependent effect of epidermal growth factor on intercellular adhesion and synthesis of triton-insoluble proteins in human carcinoma A431 cells.

    abstract::Human epidermoid carcinoma A431 cells attach more rapidly to collagen type-I and -IV substrates than to surfaces coated with laminin or fibronectin. The diminished intercellular interaction and rounding up manifested when these cells are exposed to epidermal growth factor (EGF) in tissue culture plastic or collagen fi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Rieber M,Gil F,Rieber MS,Urbina C

    更新日期:1986-03-15 00:00:00

  • Therapeutic modulators of hepatic stellate cells for hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer-related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of g...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审


    authors: Ruan Q,Wang H,Burke LJ,Bridle KR,Li X,Zhao CX,Crawford DHG,Roberts MS,Liang X

    更新日期:2020-09-15 00:00:00

  • Histologic features of bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan.

    abstract::Histologic characteristics of bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan, were evaluated. In each of these areas broadly-based series of cases were assembled during a collaborative case-control study. The present analysis was based on 589 cases in Boston, 484 cases in Manchester, and 241 cases in...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Morrison AS,Proppe KH,Verhoek WG,Aoki K,Leck I,Ohno Y,Obata K

    更新日期:1982-12-15 00:00:00

  • Fibronectin isoforms are differentially expressed in normal and adenomatous human anterior pituitaries.

    abstract::The expression of fibronectin (FN) isoforms containing the extradomains A and B (ED-A+ and ED-B+ FNs) as well as a differentially O-glycosylated oncofetal form of the protein (onf-FN) was investigated in 6 normal human anterior pituitaries and 25 human pituitary adenomas. In normal tissue, immunohistochemical experime...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Farnoud MR,Farhadian F,Samuel JL,Derome P,Peillon F,Li JY

    更新日期:1995-03-29 00:00:00

  • Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies.

    abstract::Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Pohl C,Renner C,Schwonzen M,Sieber M,Lorenz P,Pfreundschuh M,Diehl V

    更新日期:1992-04-01 00:00:00

  • Quantitative proteomics to study a small molecule targeting the loss of von Hippel-Lindau in renal cell carcinomas.

    abstract::Inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), is known to play an important role in the development of sporadic clear cell renal cell carcinomas (ccRCCs). Even if available targeted therapies for metastatic RCCs (mRCCs) have helped to improve progression-free survival rates, they have no durable ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Bouhamdani N,Joy A,Barnett D,Cormier K,Léger D,Chute IC,Lamarre S,Ouellette R,Turcotte S

    更新日期:2017-08-15 00:00:00

  • Leukaemias in BN/a and BN/b mice after prolonged treatment with antilymphocyte globulin.

    abstract::The influence of prolonged treatment with antilymphocyte globulin on tumour incidence in BN/a and BN/b mice was studied. One ALG sample appeared to be highly leukaemogenic in two independent experiments. All treated mice developed, after a short latency period, non-thymic lymphomas with involvement of abdominal lymph ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Szkudlarek J,Radzikowski C,Czarnomska A,Dux K,Bartoszewicz W

    更新日期:1976-12-15 00:00:00

  • Human gastric carcinoma transduced with the IL-2 gene: increased sensitivity to immune effector cells in vitro and in vivo.

    abstract::We transduced a human gastric carcinoma cell line, HR, with the interleukin 2 (IL-2) gene. Stable HR transfectants secreted nanogram quantities of biologically active IL-2 and had significantly increased expression of IL-2 mRNA relative to that in parental cells. Expression of intracellular IL-2 protein was not quanti...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Nagashima S,Kashii Y,Reichert TE,Suminami Y,Suzuki T,Whiteside TL

    更新日期:1997-07-03 00:00:00

  • Prexasertib (LY2606368) reduces clonogenic survival by inducing apoptosis in primary patient-derived osteosarcoma cells and synergizes with cisplatin and talazoparib.

    abstract::Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. T...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Heidler CL,Roth EK,Thiemann M,Blattmann C,Perez RL,Huber PE,Kovac M,Amthor B,Neu-Yilik G,Kulozik AE

    更新日期:2020-08-15 00:00:00

  • Reduced allergy and immunoglobulin E among adults with intracranial meningioma compared to controls.

    abstract::Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study partici...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wiemels JL,Wrensch M,Sison JD,Zhou M,Bondy M,Calvocoressi L,Black PM,Yu H,Schildkraut JM,Claus EB

    更新日期:2011-10-15 00:00:00

  • Suppression of intracellular Cu-Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells.

    abstract::We have previously described an inverse relationship between Cu-Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu-Zn SOD activity by transfection with anti-sense cDNA enhanced motility in vitro. The present studies were undertaken to dete...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tanaka M,Kogawa K,Nishihori Y,Kuribayashi K,Nakamura K,Muramatsu H,Koike K,Sakamaki S,Niitsu Y

    更新日期:1997-10-09 00:00:00

  • Characterization and partial purification of human milk fat globule membrane antigens by polyacrylamide gel electrophoresis and immunoblotting using monoclonal antibodies.

    abstract::Polyclonal and monoclonal antibodies were used to characterize human milk fat globule (HMFG) membrane antigens, using gel filtration, ion exchange chromatography and western blotting. Although originally generated against HMFG, monoclonal antibodies also reacted with skim milk. In western blotting, several antigen mol...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Ashorn P,Krohn K

    更新日期:1985-02-15 00:00:00

  • Parity and breast cancer risk: possible effect on age at diagnosis.

    abstract::We examined the effect of parity on breast cancer risk on the basis of information from 107,146 married female nurses followed prospectively between 1976-1980. For everparous women, a significant protective effect against breast cancer was observed with increasing parity (chi 12 for trend = 14.2, p less than 0.001). A...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Pathak DR,Speizer FE,Willett WC,Rosner B,Lipnick RJ

    更新日期:1986-01-15 00:00:00

  • MLL/AF10(OM-LZ)-immortalized cells expressed cytokines and induced host cell proliferation in a mouse bone marrow transplantation model.

    abstract::Several mouse models studying the MLL fusion-induced leukemic transformation showed that a myeloproliferation stage precedes leukemia or occurred as the only phenotype of hematological disorder in mice. We established 6 MLL/AF10(OM-LZ)-immortalized cell lines by retrovirally transducing the fusion gene into bone marro...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Fu JF,Hsu CL,Shih LY

    更新日期:2010-04-01 00:00:00

  • Role of the stromal microenvironment in carcinogenesis of the prostate.

    abstract::The topic of this review is the role of stromal-epithelial interactions in normal and malignant prostatic growth. Because cell-cell interactions and androgens play such key roles in the prostate, the goal of this review will be to apply endocrinologic and developmental concepts to the understanding of normal and malig...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审


    authors: Cunha GR,Hayward SW,Wang YZ,Ricke WA

    更新日期:2003-10-20 00:00:00

  • Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion.

    abstract::We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up-regulated E-cadherin, an epi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kabashima A,Higuchi H,Takaishi H,Matsuzaki Y,Suzuki S,Izumiya M,Iizuka H,Sakai G,Hozawa S,Azuma T,Hibi T

    更新日期:2009-06-15 00:00:00

  • A specific inducible nitric oxide synthase inhibitor, ONO-1714 attenuates inflammation-related large bowel carcinogenesis in male Apc(Min/+) mice.

    abstract::It is generally assumed that inflammation influences carcinogenesis. We previously reported that dextran sodium sulfate (DSS) strongly enhances colon carcinogenesis in the Apc(Min/+) mice and the over-expression of inducible nitric oxide synthase (iNOS) contributes to this enhancement. In the current study, we investi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kohno H,Takahashi M,Yasui Y,Suzuki R,Miyamoto S,Kamanaka Y,Naka M,Maruyama T,Wakabayashi K,Tanaka T

    更新日期:2007-08-01 00:00:00

  • Cytoplasmic PARP-1 promotes pancreatic cancer tumorigenesis and resistance.

    abstract::The poly(ADP-ribose) polymerases (PARP) play important roles in repairing damaged DNA during intrinsic cell death. We recently linked PARP-1 to death receptor (DR)-activated extrinsic apoptosis, the present studies sought to elucidate the function of cytoplasmic PARP-1 in pancreatic cancer tumorigenesis and therapy. U...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Xu F,Sun Y,Yang SZ,Zhou T,Jhala N,McDonald J,Chen Y

    更新日期:2019-07-15 00:00:00

  • A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

    abstract::Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (S...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究


    authors: Harlid S,Ivarsson MI,Butt S,Hussain S,Grzybowska E,Eyfjörd JE,Lenner P,Försti A,Hemminki K,Manjer J,Dillner J,Carlson J

    更新日期:2011-10-01 00:00:00

  • No excess risk for colorectal cancer among subjects seropositive for the JC polyomavirus.

    abstract::The human polyomaviruses JC virus (JCV) and BK virus (BKV) are oncogenic in experimental systems and commonly infect humans. JCV DNA has been reported to be present in human colon mucosa and in colorectal cancers. To investigate whether the risk for colorectal cancer is associated with JCV or BKV infection, we perform...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lundstig A,Stattin P,Persson K,Sasnauskas K,Viscidi RP,Gislefoss RE,Dillner J

    更新日期:2007-09-01 00:00:00