Farhat, Katja

[["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","1449"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","1460"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Schaffrinski, Meike"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-10T08:11:45Z"],["dc.date.available","2019-07-10T08:11:45Z"],["dc.date.issued","2013-09-01"],["dc.description.abstract","The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis."],["dc.identifier.fs","599082"],["dc.identifier.pmid","24036536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10758"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60792"],["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.subject.mesh","Animals"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Communication"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Coculture Techniques"],["dc.subject.mesh","Diphosphonates"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Imidazoles"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Matrix Metalloproteinases"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Tumor Microenvironment"],["dc.title","Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, H.-N."],["dc.contributor.author","vanRossum, D. V."],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, M."],["dc.contributor.author","Wenske, Britta"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:23:22Z"],["dc.date.available","2018-11-07T09:23:22Z"],["dc.date.issued","2013"],["dc.format.extent","S216"],["dc.identifier.isi","000320408400701"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29559"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","CARCINOMA CELLS MISUSE THE HOST TISSUE DANGER RESPONSE TO INVADE THE BRAIN"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]