TY  - JOUR
A1  - Herbert, Saskia-Laureen
A1  - Fick, Andrea
A1  - Heydarian, Motaharehsadat
A1  - Metzger, Marco
A1  - Wöckel, Achim
A1  - Rudel, Thomas
A1  - Kozjak-Pavlovic, Vera
A1  - Wulff, Christine
T1  - Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer
JF  - Journal of Tissue Engineering
N2  - Ovarian cancer is the second most common gynecological malignancy in women. More than 70% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer.
KW  - ovarian cancer
KW  - 3D tissue model
KW  - co-culture
KW  - peritoneal metastasis
KW  - cancer dissemination
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301311
SN  - 2041-7314
VL  - 13
ER  - 
TY  - JOUR
A1  - Vollmuth, Nadine
A1  - Schlicker, Lisa
A1  - Guo, Yongxia
A1  - Hovhannisyan, Pargev
A1  - Janaki-Raman, Sudha
A1  - Kurmasheva, Naziia
A1  - Schmitz, Werner
A1  - Schulze, Almut
A1  - Stelzner, Kathrin
A1  - Rajeeve, Karthika
A1  - Rudel, Thomas
T1  - c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis
JF  - eLife
N2  - Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism.
KW  - Chlamydia trachomatis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301385
VL  - 11
ER  -