Hagemann, Johannes

[["dc.bibliographiccitation.firstpage","98"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Annals of Hematology"],["dc.bibliographiccitation.lastpage","103"],["dc.bibliographiccitation.volume","82"],["dc.contributor.author","Schuttrumpf, S."],["dc.contributor.author","Binder, L."],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Berkovic, D."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T10:41:02Z"],["dc.date.available","2018-11-07T10:41:02Z"],["dc.date.issued","2003"],["dc.description.abstract","Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases. A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking. To evaluate the impact of PCT in this setting, PCT and CRP were prospectively measured in 95 febrile hemato-oncological patients. Infections could be identified in 40 of 95 patients: 38 of 95 had fever of unknown origin (FUO), 9 patients were suspected to suffer from drug-related fever, and 8 patients from tumor-associated fever. In the noninfection group (drug-related and tumor-associated fever), PCT levels were significantly lower than in patients with infections (P<0.001) or FUO (P<0.001). Differences were still highly significant comparing patients with suspected drug-related or tumor-associated fever alone with the infection or the FUO cohort. All eight patients with tumor-associated fever as well as eight of the nine patients with drug-related fever had PCT levels within the normal range (<0.5 mu g/l). CRP values only partially allowed discrimination between the various subgroups. Differences were significant between patients with drug-related fever and the infection (P=0.001) or FUO group (P=0.004). However, as CRP levels were far above the normal range also in the patients with drug-related fever, the significance of individual values was rather limited. In conclusion, PCT may provide useful additional information to assess the clinical significance of febrile conditions. PCT may facilitate the decision on when to initiate antimicrobial or cytotoxic therapy."],["dc.identifier.doi","10.1007/s00277-002-0584-y"],["dc.identifier.isi","000181574600007"],["dc.identifier.pmid","12601488"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46448"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0584"],["dc.relation.issn","0939-5555"],["dc.title","Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Biology of Reproduction"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Husen, B."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Einspanier, Almuth"],["dc.date.accessioned","2018-11-07T11:01:15Z"],["dc.date.available","2018-11-07T11:01:15Z"],["dc.date.issued","2000"],["dc.format.extent","260"],["dc.identifier.isi","000087862300456"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51105"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Study Reproduction"],["dc.publisher.place","Madison"],["dc.relation.issn","0006-3363"],["dc.title","Influence of progesterone, estradiol and relaxin on uterine differentiation in ovariectomized marmoset monkeys."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","157"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Breast Cancer Research and Treatment"],["dc.bibliographiccitation.lastpage","166"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Simon, Alfred"],["dc.contributor.author","Binder, L."],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Emons, G."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Einspanier, Almuth"],["dc.date.accessioned","2018-11-07T10:45:48Z"],["dc.date.available","2018-11-07T10:45:48Z"],["dc.date.issued","2004"],["dc.description.abstract","Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up. RLX concentrations in cancer patients were significantly higher than in a control population of healthy blood donors and patients with various other diseases (0.47 versus 0.29 ng/ml, p < 0.0001). There was a significant difference between patients with metastases (0.62 ng/ml) and those without (0.38 ng/ml, p < 0.0001). Overall survival was shorter in RLX-positive (>0.4 ng/ml) than in RLX-negative patients (p = 0.016). Cox regression analysis showed that RLX was not an independent variable, in contrast to metastatic disease and primary lymph node involvement. Taken together, the detection of elevated RLX concentrations especially in patients with metastases supports the assumption that there is a role for RLX in tissue remodeling during breast cancer progression."],["dc.identifier.doi","10.1023/B:BREA.0000041622.30169.16"],["dc.identifier.isi","000223914900005"],["dc.identifier.pmid","15377840"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47592"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Kluwer Academic Publ"],["dc.relation.issn","0167-6806"],["dc.title","Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","766"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","DNA and Cell Biology"],["dc.bibliographiccitation.lastpage","776"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Binder, L."],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Grimshaw, M. J."],["dc.date.accessioned","2018-11-07T10:54:33Z"],["dc.date.available","2018-11-07T10:54:33Z"],["dc.date.issued","2005"],["dc.description.abstract","There is increased staining of endothelins (ET-1, - 2, and - 3) and receptors (ET-RA and - RB) in invasive breast tumors compared to nonneoplastic tissue, and ETs stimulate MCF-7 cell invasion in vitro. We analyzed ET-stimulation of benign and transformed mammary epithelial cells, and whether expression of ETs is sufficient to induce invasiveness. In breast cancer patient serum, ET-1 was increased in those patients with lymph node metastases compared to those with no lymph node involvement; ETs, however, had no mitogenic effect on breast tumor cell lines in vitro. The benign mammary epithelial cell line, hTERT-HME1, and the poorly invasive breast tumor cell line MCF-7 secreted low levels of ET-1, while the invasive cell lines SKBR3 and MDAMB231 secreted high levels. Expression of the ETs and receptors by the cell lines broadly correlated with their in vitro invasiveness; overexpression of ETs in MCF-7 cells increased basal invasion. ET-mediated invasion involved both receptors and a calcium influx to induce a pertussis toxin-sensitive MAPK pathway. MMP-14 activity was induced via ET-RA in an autocrine manner. In contrast to transformed cells, ET stimulation or overexpression did not induce an invasive phenotype in benign cells. Benign cells do not respond to ETs, and ET expression is not sufficient to induce invasion; however, the level of ET production by tumor cells correlates with their invasiveness, and increasing expression of the ET axis promotes breast tumor cell invasion via both receptors, while MMP-14 is induced via ET-RA."],["dc.identifier.doi","10.1089/dna.2005.24.766"],["dc.identifier.isi","000233319900008"],["dc.identifier.pmid","16274297"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49590"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mary Ann Liebert Inc"],["dc.relation.issn","1044-5498"],["dc.title","Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1839"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","European Journal of Cancer"],["dc.bibliographiccitation.lastpage","1846"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Gunawan, Bastian"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T08:34:30Z"],["dc.date.available","2018-11-07T08:34:30Z"],["dc.date.issued","2001"],["dc.description.abstract","Altered expression of matrix metalloproteases (MMPs) and their inhibitors, the tissue inhibitors of matrix metalloproteases (TIMPs), has been demonstrated in various tumour tissues. mRNA expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-12, MMP-14 and TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 30 renal cell carcinomas (RCC), as well as in the surrounding tissues. Expression of the MMPs was significantly stronger in the carcinomas than in non-malignant tissues. High levels were demonstrated particularly in clear cell RCCs (CC-RCC). Except for MMP-1, MMP expression in the papillary RCCs (P-RCC) was, for most MMPs, significantly lower. Expression of the TIMPs in malignant cells of both subtypes was weak, with the exception of TIMP-4 which was strongly expressed in the P-RCCs and downregulated in the CC-RCCs. The latter was correlated with chromosomal loss of 3p, harbouring the TIMP-4 gene locus. In conclusion, deregulated expression of the MMPs and TIMPs in RCCs differs according to histology, grade, size and cytogenetic characteristics, suggesting that MMP and TIMP expression patterns play an important role for the typical histomorphological features of RCC subtypes and their respective biological behaviour. (C) 2001 Published by Elsevier Science Ltd."],["dc.identifier.doi","10.1016/S0959-8049(01)00215-5"],["dc.identifier.isi","000171188500016"],["dc.identifier.pmid","11576837"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17833"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0959-8049"],["dc.title","MRNA expression of matrix metalloproteases and their inhibitors differs in subtypes of renal cell carcinomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1197"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","1205"],["dc.bibliographiccitation.volume","175"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Wilson, Julianna K."],["dc.contributor.author","Kulbe, H."],["dc.contributor.author","Li, NFF"],["dc.contributor.author","Leinster, D. A."],["dc.contributor.author","Charles, K."],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Balkwill, F. R."],["dc.date.accessioned","2018-11-07T08:40:35Z"],["dc.date.available","2018-11-07T08:40:35Z"],["dc.date.issued","2005"],["dc.description.abstract","Tumor-associated macrophages may influence tumor progression, angiogenesis and invasion. To investigate mechanisms by which macrophages interact with tumor cells, we developed an in vitro coculture model. Previously we reported that coculture enhanced invasiveness of the tumor cells in a TNF-alpha- and matrix metalloprotease-dependent manner. In this report, we studied intracellular signaling pathways and induction of inflammatory genes in malignant cells under the influence of macrophage coculture. We report that coculture of macrophages with ovarian or breast cancer cell lines led to TNF-alpha-dependent activation of JNK and NF-kappa B pathways in tumor cells, but not in benign immortalized epithelial cells. Tumor cells with increased JNK and NF-kappa B activity exhibited enhanced invasiveness. Inhibition of the NF-kappa B pathway by TNF-alpha neutralizing Abs, an NF-kappa B inhibitor, RNAi to Re1A, or overexpression of I kappa B inhibited tumor cell invasiveness. Blockade of JNK also significantly reduced invasiveness, but blockade of p38 MAPK or p42 MAPK had no effect. Cocultured tumor cells were screened for the expression of 22 genes associated with inflammation and invasion that also contained an AP-1 and NF-kappa B binding site. EMMPRIN and MIF were up-regulated in cocultured tumor cells in a JNK- and NF-kappa B-dependent manner. Knocking down either MIF or EMMPRIN by RNAi in the tumor cells significantly reduced tumor cell invasiveness and matrix metalloprotease activity in the coculture supernatant. We conclude that TNF-alpha, via NF-kappa B, and JNK induces MIF and EMMPRIN in macrophage to tumor cell cocultures and this leads to increased invasive capacity of the tumor cells."],["dc.identifier.isi","000233647600067"],["dc.identifier.pmid","16002723"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19268"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","789"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","MHR Basic science of reproductive medicine"],["dc.bibliographiccitation.lastpage","796"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Husen, B."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Einspanier, Almuth"],["dc.date.accessioned","2018-11-07T10:07:56Z"],["dc.date.available","2018-11-07T10:07:56Z"],["dc.date.issued","2002"],["dc.description.abstract","Until recently, relaxin (RLX) has been known predominantly for its effects on the reproductive system, where it induces remodelling of the extracellular matrix and up-regulation of matrix metalloproteases (MMPs). In solid cancers, tissue remodelling and MNIP activation are essential for invasion and metastasis. We therefore investigated the effect of RLX on invasiveness and MNIP expression of human breast cancer cell lines. Upon incubation with porcine RLX, the invasiveness of SK-BR3 cells was significantly increased. Similar effects could be achieved in MCF-7 cells, especially when RLX was combined with epidermal growth factor. Enhanced invasiveness was accompanied by up-regulation of NIMP production and could be almost completely blocked by the NIMP inhibitor FN 439. Zymography revealed increased secretion of MMP-2, -7 and -9, associated with upregulated mRNA concentrations of MMP-2, -9, -13 and -14. mRNA expression levels of MMP-1, -3, -7, -8, -10, -11, -12 and of tissue inhibitors of metalloproteases-1, -2, -3 and -4 were either very low or not detectably influenced by RLX. Taken together, RLX enhances in-vitro invasiveness of breast cancer cell lines by induction of MMP expression. It remains to be clarified whether RLX might play a similar role in vivo and promote tumour progression."],["dc.identifier.doi","10.1093/molehr/8.9.789"],["dc.identifier.isi","000177970900001"],["dc.identifier.pmid","12200455"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39378"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1360-9947"],["dc.title","Relaxin enhances in-vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2461"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","2468"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Grimshaw, M. J."],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Ayhan, A."],["dc.contributor.author","Gillett, C. E."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Balkwill, F. R."],["dc.date.accessioned","2018-11-07T10:49:46Z"],["dc.date.available","2018-11-07T10:49:46Z"],["dc.date.issued","2004"],["dc.description.abstract","We have studied the role of endothelins (ET-1, ET-2 and ET-3) and ET receptors (ET-RA and ET-RB) in the invasive capacity of breast tumor cells, which express ET-I and ET-2 as well as ET-RA and ET-RB. Of five human breast tumor cell lines tested, all expressed mRNAs for ET-1, ET-2, and ET-RB. ET-RA mRNA was expressed by four of five tumor cell lines. Breast tumor cells migrated toward ET-I and ET-2 but not toward ET-3. Chemotaxis involved signaling via both receptors, and a pertussis toxin-sensitivep42/p44mitogen-activated protein kinase (MAPK)mediated pathway that could be inhibited by MAPK kinase (MEK)1/2 antagonists. Chemotaxis toward ETs did not involve p38 or stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) and was not inhibited by hypoxia. Incubation of tumor cells with ET-2 also increased chemotaxis toward the chemokines CXCL12 and CCL21. As well as inducing chemotaxis of tumor cells, ET-1 and ET-2 increased tumor cell invasion through Matrigel. Furthermore, stimulation of macrophage/tumor cell cocultures with ETs led to increased matrix metalloproteinase (MMP)-2 and -9 production by macrophages and a marked increase in invasion of tumor cells. Antagonism of either ET-RA or ET-RB decreased the invasion seen in ET-stimulated cocultures, as did a broad-spectrum MMP inhibitor. Immunohistochemical staining of human breast tumor sections showed increased ET and ET receptor protein expression by tumor cells in invasive ductal carcinoma compared with normal breast tissue or ductal carcinoma in situ. Furthermore, tumor cell ET and receptor expression was stronger at the invasive margin of invasive ductal carcinomas, in the lymphovascular space, and in lymph node metastases. ET expression often colocalized with ET-RB expression in all neoplastic tissue indicating a possible autocrine action of ETs. We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells."],["dc.identifier.doi","10.1158/0008-5472.CAN-03-1069"],["dc.identifier.isi","000220586500023"],["dc.identifier.pmid","15059899"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48508"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.title","A role for endothelin-2 and its receptors in breast tumor cell invasion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1543"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1549"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Robinson, S. C."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Balkwill, F. R."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T10:46:34Z"],["dc.date.available","2018-11-07T10:46:34Z"],["dc.date.issued","2004"],["dc.description.abstract","Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages."],["dc.identifier.doi","10.1093/carcin/bgh146"],["dc.identifier.isi","000223142700027"],["dc.identifier.pmid","15044327"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47775"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5454"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","5459"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Gradl, D."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Siemes, S."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T09:59:40Z"],["dc.date.available","2018-11-07T09:59:40Z"],["dc.date.issued","2006"],["dc.description.abstract","Interactions between neoplastic and stromal cells contribute to tumor progression. Wnt genes, involved in cell migration and often deregulated in cancers, are attractive candidates to regulate these effects. We have recently shown that coculture of breast cancer cells with macrophages enhances invasiveness via matrix metal loproteases and TNF-alpha. Here we demonstrate that coculture of MCF-7 cells and macrophages leads to up-regulation of Writ 5a in the latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant Writ 5a mimicked the coculture effect. Writ 5a was also detectable in tumor-associated macrophages in primary breast cancers. Experiments with agonists and antagonists of Writ signaling revealed that a functional canonical pathway in the tumor cells was a necessary prerequisite; however, noncanonical signaling via Writ 5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was also responsible for induction of matrix metalloprotease-7, known to release TNF-alpha. All these effects could be antagonized by dickkopf-1. Our results indicate that Wnt 5a is essential for macrophage-induced invasiveness, because it regulates tumor cell migration as well as proteolytic activity of the macrophages. The function of Writ 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions. Writ 5a detection in tumor-associated macrophages in breast cancer biopsies supports the assumption that similar events play a role in vivo."],["dc.description.sponsorship","Medical Research Council [G0601867]"],["dc.identifier.doi","10.1073/pnas.0509703103"],["dc.identifier.isi","236636400040"],["dc.identifier.pmid","16569699"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37646"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]