TY  - JOUR
AB  - CRN2 is an actin filament binding protein involved in the regulation of various cellular processes including cell migration and invasion. CRN2 has been implicated in the malignant progression of different types of human cancer. We used CRN2 knock-out mice for analyses as well as for crossbreeding with a Tp53/Pten knock-out glioblastoma mouse model. CRN2 knock-out mice were subjected to a phenotyping screen at the German Mouse Clinic. Murine glioblastoma tissue specimens as well as cultured murine brain slices and glioblastoma cell lines were investigated by immunohistochemistry, immunofluorescence, and cell biological experiments. Protein interactions were studied by immunoprecipitation, pull-down, and enzyme activity assays. CRN2 knock-out mice displayed neurological and behavioural alterations, e.g. reduced hearing sensitivity, reduced acoustic startle response, hypoactivity, and less frequent urination. While glioblastoma mice with or without the additional CRN2 knock-out allele exhibited no significant difference in their survival rates, the increased levels of CRN2 in transplanted glioblastoma cells caused a higher tumour cell encasement of murine brain slice capillaries. We identified two important factors of the tumour microenvironment, the tissue inhibitor of matrix metalloproteinase 4 (TIMP4) and the matrix metalloproteinase 14 (MMP14, synonym: MT1-MMP), as novel binding partners of CRN2. All three proteins mutually interacted and co-localised at the front of lamellipodia, and CRN2 was newly detected in exosomes. On the functional level, we demonstrate that CRN2 increased the secretion of TIMP4 as well as the catalytic activity of MMP14. Our results imply that CRN2 represents a pro-invasive effector within the tumour cell microenvironment of glioblastoma multiforme.
AU  - Solga, R.*
AU  - Behrens, J.*
AU  - Ziemann, A.*
AU  - Riou, A.*
AU  - Berwanger, C.*
AU  - Becker, L.
AU  - Garrett, L.
AU  - Hrabě de Angelis, M.
AU  - Fischer, L.*
AU  - Coras, R.*
AU  - Barkovits, K.*
AU  - Marcus, K.*
AU  - Mahabir, E.*
AU  - Eichinger L*
AU  - Schröder, R.*
AU  - Noegel, A.A.*
AU  - Clemen, C.S.*
AU  - German Mouse Clinic Consortium (Aguilar-Pimentel, J.A.
AU  - Schmidt-Weber, C.B.
AU  - Adler, T.
AU  - Treise, I.
AU  - Moreth, K.
AU  - Hölter, S.M.
AU  - Zimprich, A.
AU  - Wurst, W.*
AU  - Amarie, O.V.
AU  - Graw, J.
AU  - Rozman, J.
AU  - Calzada-Wack, J.
AU  - Rathkolb, B.
AU  - Östereicher, M.A.
AU  - Miller, G.
AU  - Lengger, C.
AU  - Maier, H.
AU  - Stoeger, C.
AU  - Leuchtenberger, S.
AU  - Gailus-Durner, V.
AU  - Fuchs, H.)
C1  - 57107
C2  - 47539
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - CRN2 binds to TIMP4 and MMP14 and promotes perivascular invasion of glioblastoma cells.
JO  - Eur. J. Cell Biol.
VL  - 98
IS  - 5-8
PB  - Elsevier Gmbh
PY  - 2019
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - This review summarizes our studies of the past several years on the development of third generation dendritic cell (DC) vaccines. These developments have implemented two major innovations in DC preparation: first, young DCs are prepared within 3days and, second, the DCs are matured with the help of Toll-like receptor agonists, imbuing them with the capacity to produce bioactive IL-12 (p70). Based on phenotype, chemokine-directed migration, facility to process and present antigens, and stimulatory capacity to polarize Th1 responses in CD4(+) T cells, induce antigen-specific CD8(+) CTL and activate natural killer cells, these young mDCs display all the important properties needed for initiating good antitumor responses in a vaccine setting.
AU  - Frankenberger, B.
AU  - Schendel, D.J.
C1  - 6615
C2  - 28979
SP  - 53-58
TI  - Third generation dendritic cell vaccines for tumor immunotherapy.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Heat shock proteins (Hsps) hold a dual role depending on their location. Inside cells, they fulfill essential survival functions as molecular chaperones forming complexes with intracellular polypeptides (self or foreign) to help in protein folding, the resolution of protein aggregates and intracellular protein transport. Released from the cell, they act as messengers communicating the cells' interior protein composition to the immune system for initiation of immune responses against intracellular proteins. Here we describe the mechanisms by which Hsp70, the heat-inducible Hsp70 family member, crosstalks with the immune system. Further, we discuss that clinical hyperthermia could be a way to initiate the immunologic activity of Hsp70 by upregulating its expression and facilitating release through local necrosis.
AU  - Jolesch, A.
AU  - Elmer, K.
AU  - Bendz, H.
AU  - Issels, R.D.
AU  - Nößner, E.
C1  - 6640
C2  - 29020
SP  - 48-52
TI  - Hsp70, a messenger from hyperthermia for the immune system.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Over the last 25 years, remarkable progress has been made not only in identifying key molecules of Alzheimer's disease but also in understanding their meaning in the pathogenic state. One hallmark of Alzheimer pathology is the amyloid plaque. A major component of the extracellular deposit is the amyloid-beta (A beta) peptide which is generated from its larger precursor molecule, i.e., the amyloid precursor protein (APP) by consecutive cleavages. Processing is exerted by two enzymes, i.e., the beta-secretase and the gamma-secretase. We and others have found that the self-association of the amyloid peptide and the dimerization and oligomerization of these proteins is a key factor under native and pathogenic conditions. In particular, the A beta homodimer represents a nidus for plaque formation and a well defined therapeutic target. Further, dimerization of the APP was reported to increase generation of toxic A beta whereas heterodimerization with its homologues amyloid precursor like proteins (APLP1 and APLP2) decreased A beta formation. This review mainly focuses on structural features of the homophilic and heterophilic interactions among APP family proteins. The proposed contact sites are described and the consequences of protein dimerization on their functions and in the pathogenesis of Alzheimer's disease are discussed.
AU  - Kaden, D.*
AU  - Munter, L.M.*
AU  - Reif, B.
AU  - Multhaup, G.*
C1  - 8032
C2  - 29963
SP  - 234-239
TI  - The amyloid precursor protein and its homologues: Structural and functional aspects of native and pathogenic oligomerization.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 4
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Epstein-Barr virus (EBV) is a human tumor virus and a paradigm of herpesviral latency. Mature naïve or memory B cells are EBV's preferred targets in vitro and in vivo. Upon infection of any B cell with EBV, the virus induces cellular proliferation to yield lymphoblastoid cell lines (LCLs) in vitro and establishes a latent infection in them. In these cells a 'classical' subset of latent viral genes is expressed that orchestrate and regulate cellular activation and proliferation, prevent apoptosis, and maintain viral latency. Surprisingly, little is known about the early events in primary human B cells infected with EBV. Recent analyses have revealed the initial but transient expression of additional viral genes that do not belong to the 'classical' latent subset. Some of these viral genes have been known to initiate the lytic, productive phase of EBV but virus synthesis does not take place early after infection. The early but transient expression of certain viral lytic genes is essential for or contributes to the initial survival and cell cycle entry of resting B cells to foster their proliferation and sustain a latent infection. This review summarizes the recent findings and discusses the presumed function(s) of viral genes expressed shortly but transiently after infection of B-lymphocytes with EBV.
AU  - Kalla, M.
AU  - Hammerschmidt, W.
C1  - 6660
C2  - 29058
CY  - Jena, Germany
SP  - 65-69
TI  - Human B cells on their route to latent infection - early but transient expression of lytic genes of Epstein-Barr virus.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Epstein-Barr virus (EBV) establishes lifelong persistent infections in humans and has been implicated in the pathogenesis of several human malignancies. Protective immunity against EBV is mediated by T cells, as indicated by an increased incidence of EBV-associated malignancies in immunocompromised patients, and by the successful treatment of EBV-associated post-transplant lymphoproliferative disease (PTLD) in transplant recipients by the infusion of polyclonal EBV-specific T cell lines. To implement this treatment modality as a conventional therapeutic option, and to extend this protocol to other EBV-associated diseases, generic and more direct approaches for the generation of EBV-specific T cell lines enriched in disease-relevant specificities need to be developed. To this aim, we studied the poorly defined EBV-specific CD4+ T cell response during acute and chronic infection.
AU  - Mautner, J.
AU  - Bornkamm, G.W.
C1  - 6655
C2  - 29050
SP  - 31-35
TI  - The role of virus-specific CD4+ T cells in the control of Epstein-Barr virus infection.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Adoptive T cell therapy is the transfer of T cells to a patient in order to combat disease. This procedure is mainly being used but not limited to the treatment of viral infections and malignancies including virus-associated tumors. Depending on the clinical context, the T cell donor may be the same patient or another donor, usually a healthy person. Recent research is centered on the use of antigen-specific T cells, but T cells of uncharacterized specificity can be successfully used in some clinical conditions where target antigens are not known. Depending on underlying scientific hypotheses and preferred technologies, the therapeutic T cells may be anything from monoclonal to highly polyclonal; they may be specific for one epitope, several epitopes from one antigen, or various antigens; they may have been selected during the preparation process for their specificity, their functional capacity, their survival and proliferation in vitro, or the expression of surface markers associated with desirable functional properties. In this minireview, we give a brief overview on selected approaches, problems and solutions in adoptive T cell therapy. We focus on an area where T cell therapy has been particularly successful but is still calling for improvement: herpesviral disease in patients after transplantation.
AU  - Moosmann, A.
AU  - Hammerschmidt, W.
AU  - Kolb, H.-J.*
C1  - 6659
C2  - 29057
CY  - Jena, Germany
SP  - 97-101
TI  - Virus-specific T cells for therapy - approaches, problems, solutions.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  - 

TY  - JOUR
AB  - Early detection of viruses by the innate immune system is critical for host defense. Antiviral immunity is initiated by germline encoded pattern recognition receptors (PRRs) that recognize viral pathogen-associated molecular patterns (PAMPs) such as nucleic acids. Intracellular PRRs then drive the production of interferons and cytokines to orchestrate immune responses. One key host factor that is critical for antiviral immunity and for systemic inflammatory reactions including fever is interleukin-1beta (IL-1β). Here we discuss current insights into the molecular mechanisms how the cytosolic RNA helicase RIG-I triggers NF-κB signaling and inflammasome activation specifically for RNA virus-induced IL-1β production.
AU  - Poeck, H.*
AU  - Ruland, J.
C1  - 6348
C2  - 29046
CY  - Jena, Germany
SP  - 59-64
TI  - From virus to inflammation: Mechanisms of RIG-I-induced IL-1β production.
JO  - Eur. J. Cell Biol.
VL  - 91
IS  - 1
PB  - Elsevier
PY  - 2012
SN  - 0171-9335
ER  -