Bleckmann, Annalen

[["dc.bibliographiccitation.artnumber","135"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2019-07-09T11:43:27Z"],["dc.date.available","2019-07-09T11:43:27Z"],["dc.date.issued","2017"],["dc.description.abstract","Breast cancer is a heterogeneous disease and has been classified into five molecular subtypes based on gene expression profiles. Signaling processes linked to different breast cancer molecular subtypes and different clinical outcomes are still poorly understood. Aberrant regulation of Wnt signaling has been implicated in breast cancer progression. In particular Ror1/2 receptors and several other members of the non-canonical Wnt signaling pathway were associated with aggressive breast cancer behavior. However, Wnt signals are mediated via multiple complex pathways, and it is clinically important to determine which particular Wnt cascades, including their domains and targets, are deregulated in poor prognosis breast cancer. To investigate activation and outcome of the Ror2-dependent non-canonical Wnt signaling pathway, we overexpressed the Ror2 receptor in MCF-7 and MDA-MB231 breast cancer cells, stimulated the cells with its ligand Wnt5a, and we knocked-down Ror1 in MDA-MB231 cells. We measured the invasive capacity of perturbed cells to assess phenotypic changes, and mRNA was profiled to quantify gene expression changes. Differentially expressed genes were integrated into a literature-based non-canonical Wnt signaling network. The results were further used in the analysis of an independent dataset of breast cancer patients with metastasis-free survival annotation. Overexpression of the Ror2 receptor, stimulation with Wnt5a, as well as the combination of both perturbations enhanced invasiveness of MCF-7 cells. The expression-responsive targets of Ror2 overexpression in MCF-7 induced a Ror2/Wnt module of the non-canonical Wnt signaling pathway. These targets alter regulation of other pathways involved in cell remodeling processing and cell metabolism. Furthermore, the genes of the Ror2/Wnt module were assessed as a gene signature in patient gene expression data and showed an association with clinical outcome. In summary, results of this study indicate a role of a newly defined Ror2/Wnt module in breast cancer progression and present a link between Ror2 expression and increased cell invasiveness."],["dc.identifier.doi","10.3389/fonc.2017.00135"],["dc.identifier.pmid","28695110"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58892"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2234-943X"],["dc.relation.issn","2234-943X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Ror2 Signaling and Its Relevance in Breast Cancer Progression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","471"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","482"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Wegner, Christiane"],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Stadelmann, Chr."],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:26:31Z"],["dc.date.available","2018-11-07T09:26:31Z"],["dc.date.issued","2013"],["dc.description.abstract","An essential function of the transcription factors LEF1/TCF4 in cerebral metastases of lung adenocarcinomas has been described in mouse models, suggesting a WNT/beta-catenin effect as potential mechanism. Their role in humans is still unclear, thus we analyzed LEF1, TCF4, beta-catenin, and early stage prognostic markers in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). IHC revealed nuclear TCF4 in all adenocarcinoma samples, whereas only 36 % depicted nuclear LEF1 and nuclear beta-catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p = 0.01, HR = 6.68), while nuclear beta-catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. High proliferation index Ki67 was associated with shorter survival in late-stage disease (p = 0.03, HR 3.27). Additionally, we generated a LEF1/TCF4 as well as an AXIN2 signature, the latter as representative of WNT/beta-catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma. To analyze the prognostic relevance in primary lung adenocarcinomas, we applied both signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p = 0.01, HR = 0.32). These clusters displayed diverging enrichment patterns of the cell cycle pathway. In conclusion, our data show that LEF1/TCF4, but not beta-catenin, have prognostic relevance in primary and cerebrally metastasized human lung adenocarcinomas. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of beta-catenin in this setting."],["dc.identifier.doi","10.1007/s10585-012-9552-7"],["dc.identifier.isi","000317297400011"],["dc.identifier.pmid","23224985"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-7276"],["dc.relation.issn","0262-0898"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear beta-catenin in cerebral metastasis of lung adenocarcinomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","285"],["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.lastpage","286"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T09:34:18Z"],["dc.date.available","2018-11-07T09:34:18Z"],["dc.date.issued","2014"],["dc.identifier.isi","000343816900702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32144"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","EMMPRIN/CD147-positive tumor cell microvesicles are pro-invasive and detectable in the blood of cancer patients with metastasis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T08:52:16Z"],["dc.date.available","2018-11-07T08:52:16Z"],["dc.date.issued","2011"],["dc.format.extent","151"],["dc.identifier.isi","000295160600393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22130"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","LEF1 identifies a prognostically unfavourable subgroup of lung adenocarcinoma brain metastases"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Artmann, Stephan"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Klemm, E."],["dc.date.accessioned","2018-11-07T09:19:06Z"],["dc.date.available","2018-11-07T09:19:06Z"],["dc.date.issued","2013"],["dc.identifier.isi","000326360900431"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28557"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.title","Identification of prognostic miRNAs in breast cancer through profiling of tumor educated macrophages"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","143"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular Cell Biology"],["dc.bibliographiccitation.lastpage","153"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Rost, Ulrike"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Dhople, Vishnu M."],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:58:48Z"],["dc.date.available","2018-11-07T09:58:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologousand heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN."],["dc.description.sponsorship","Deutsche Krebshilfe [109615]; DFG [BI 703/3-2]; eBIO MetastaSys (BMBF)"],["dc.identifier.doi","10.1093/jmcb/mju047"],["dc.identifier.isi","000355232100006"],["dc.identifier.pmid","25503107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37445"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1759-4685"],["dc.relation.issn","1674-2788"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, M."],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2018-11-07T09:04:54Z"],["dc.date.available","2018-11-07T09:04:54Z"],["dc.date.issued","2012"],["dc.format.extent","65"],["dc.identifier.isi","000310766700159"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25203"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","Analyzing breast-cancer gene expression data using a newly developed graph-based WNT model in breast cancer"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1331"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1346"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, Michaela"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:21:57Z"],["dc.date.available","2018-11-07T09:21:57Z"],["dc.date.issued","2013"],["dc.description.abstract","The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. GLIA 2013;61:1331-1346"],["dc.identifier.doi","10.1002/glia.22518"],["dc.identifier.isi","000321983400011"],["dc.identifier.pmid","23832647"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29226"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Carcinoma cells misuse the host tissue damage response to invade the brain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1037"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neurochirurgica"],["dc.bibliographiccitation.lastpage","1045"],["dc.bibliographiccitation.volume","161"],["dc.contributor.author","Fiss, Ingo"],["dc.contributor.author","Hussein, Abdelhalim"],["dc.contributor.author","Barrantes-Freer, Alonso"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Hernandez-Duran, Silvia"],["dc.contributor.author","Wolfert, Christina"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Ninkovic, Milena"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Rohde, Veit"],["dc.contributor.author","Mielke, Dorothee"],["dc.contributor.author","Schatlo, Bawarjan"],["dc.date.accessioned","2020-12-10T14:10:53Z"],["dc.date.available","2020-12-10T14:10:53Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00701-019-03842-3"],["dc.identifier.eissn","0942-0940"],["dc.identifier.issn","0001-6268"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70910"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Cerebral metastases: do size, peritumoral edema, or multiplicity predict infiltration into brain parenchyma?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Kirchner, Benjamin"],["dc.contributor.author","Nietert, Manuel"],["dc.contributor.author","Peeck, Micha"],["dc.contributor.author","Balkenhol, Marko"],["dc.contributor.author","Egert, Daniela"],["dc.contributor.author","Rohde, T. Veit"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2021-04-14T08:31:20Z"],["dc.date.available","2021-04-14T08:31:20Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1186/s12885-020-07459-z"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83564"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1471-2407"],["dc.title","Impact of pre-OP independence in patients with limited brain metastases on long-term survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]