Menck, Kerstin

[["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","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","35"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:04:54Z"],["dc.date.available","2018-11-07T09:04:54Z"],["dc.date.issued","2012"],["dc.format.extent","195"],["dc.identifier.isi","000310766700508"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25205"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","Breast cancer invasion mediated by plasma membrane-derived microvesicles is EMMPRIN-dependent"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","33"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T08:38:50Z"],["dc.date.available","2018-11-07T08:38:50Z"],["dc.date.issued","2010"],["dc.format.extent","199"],["dc.identifier.isi","000282988401115"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18852"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","Tumor-Microparticles mediate invasiveness and elicit a M2-response in macrophages"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e51554"],["dc.bibliographiccitation.issue","91"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Behme, Daniel"],["dc.contributor.author","Pantke, Mathias"],["dc.contributor.author","Reiling, Norbert"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:35:29Z"],["dc.date.available","2018-11-07T09:35:29Z"],["dc.date.issued","2014"],["dc.description.abstract","Human macrophages are involved in a plethora of pathologic processes ranging from infectious diseases to cancer. Thus they pose a valuable tool to understand the underlying mechanisms of these diseases. We therefore present a straightforward protocol for the isolation of human monocytes from buffy coats, followed by a differentiation procedure which results in high macrophage yields. The technique relies mostly on commonly available lab equipment and thus provides a cost and time effective way to obtain large quantities of human macrophages. Briefly, buffy coats from healthy blood donors are subjected to a double density gradient centrifugation to harvest monocytes from the peripheral blood. These monocytes are then cultured in fluorinated ethylene propylene (FEP) Teflon-coated cell culture bags in the presence of macrophage colony-stimulating factor (M-CSF). The differentiated macrophages can be easily harvested and used for subsequent studies and functional assays. Important methods for quality control and validation of the isolation and differentiation steps will be highlighted within the protocol. In summary, the protocol described here enables scientists to routinely and reproducibly isolate human macrophages without the need for cost intensive tools. Furthermore, disease models can be studied in a syngeneic human system circumventing the use of murine macrophages."],["dc.identifier.doi","10.3791/51554"],["dc.identifier.isi","000349301100015"],["dc.identifier.pmid","25226391"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32396"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Journal Of Visualized Experiments"],["dc.relation.issn","1940-087X"],["dc.title","Isolation of Human Monocytes by Double Gradient Centrifugation and Their Differentiation to Macrophages in Teflon-coated Cell Culture Bags"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2057"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","2066"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Gross, Julia Christina"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2019-07-10T08:11:46Z"],["dc.date.available","2019-07-10T08:11:46Z"],["dc.date.issued","2013-11-01"],["dc.description.abstract","Recently, we have shown that macrophage (MΦ)-induced invasion of breast cancer cells requires upregulation of Wnt 5a in MΦ leading to activation of β-Catenin-independent Wnt signaling in the tumor cells. However, it remained unclear, how malignant cells induce Wnt 5a in MΦ and how it is transferred back to the cancer cells. Here we identify two types of extracellular particles as essential for this intercellular interaction in both directions. Plasma membrane-derived microvesicles (MV) as well as exosomes from breast cancer cells, although biologically distinct populations, both induce Wnt 5a in MΦ. In contrast, the particle-free supernatant and vesicles from benign cells, such as platelets, have no such effect. Induction is antagonized by the Wnt inhibitor Dickkopf-1. Subsequently, Wnt 5a is shuttled via responding MΦ-MV and exosomes to the tumor cells enhancing their invasion. Wnt 5a export on both vesicle fractions depends at least partially on the cargo protein Evenness interrupted (Evi). Its knockdown leads to Wnt 5a depletion of both particle populations and reduced vesicle-mediated invasion. In conclusion, MV and exosomes are critical for MΦ-induced invasion of cancer cells since they are responsible for upregulation of MΦ-Wnt 5a as well as for its delivery to the recipient cells via a reciprocal loop. Although of different biogenesis, both populations share common features regarding function and Evi-dependent secretion of non-canonical Wnts."],["dc.identifier.fs","603831"],["dc.identifier.pmid","24185202"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60794"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/3.0"],["dc.title","Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","323"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Schmick, Nadine Annette"],["dc.contributor.author","Schubert, Antonia"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Arackal, Jetcy"],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Schambony, Alexandra"],["dc.contributor.author","Liersch, Torsten"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T10:16:24Z"],["dc.date.available","2018-11-07T10:16:24Z"],["dc.date.issued","2016"],["dc.description.abstract","Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, beta-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the beta-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed beta-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis."],["dc.identifier.doi","10.1007/s10585-016-9780-3"],["dc.identifier.isi","000373005900002"],["dc.identifier.pmid","26862065"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41033"],["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","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","beta-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases"],["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","34"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T08:52:16Z"],["dc.date.available","2018-11-07T08:52:16Z"],["dc.date.issued","2011"],["dc.format.extent","60"],["dc.identifier.isi","000295160600152"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22127"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","0378-584X"],["dc.title","Identification and further characterization of microparticle populations in microparticle-induced breast cancer invasion"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1340745"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Extracellular Vesicles"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Wachter, Astrid"],["dc.contributor.author","Hennies, Bianca"],["dc.contributor.author","Ries, Lena"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Balkenhol, Marko"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Schatlo, Bawarjan"],["dc.contributor.author","Rost, Ulrike"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2020-12-10T18:15:29Z"],["dc.date.available","2020-12-10T18:15:29Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1080/20013078.2017.1340745"],["dc.identifier.eissn","2001-3078"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74861"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Characterisation of tumour-derived microvesicles in cancer patients’ blood and correlation with clinical outcome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]