Today, Rosa Schmuck received the 2012 Charité Robert-Koch-Prize for her doctoral thesis entitled „Genotypic and phenotypic characterization of side population of gastric cancer cell lines“ (group of Prof. C. Röcken).

The Side Population (SP) of tumor cell lines shares characteristics with tumor stem cells. In this study we phenotypically and genotypically characterized the SP of gastric cancer cell lines. SPs were obtained from MKN45- and AGS-gastric cancer cells using Hoechst 33342 staining and fluorescence-activated cell sorting (FACS). SP cells were subsequently studied morphologically (cytology, immunocytochemistry), on the transcriptional level (gene array) and in cell culture (recultivation assays). Genes differentially expressed in the SP cells were evaluated by immunohistochemistry in tissue from gastric cancer patients. SP cells were smaller and rounder then Non-SP cells. SP cells self-renewed in re-cultivation experiments and differentiated into SP- and Non-SP cells. Re-cultivated SP- and Non-SP cells showed distinct phenotypes in culture regarding cell shape and colony-formation. SP cells had increased levels of the stem cell markers CD133 and Musashi1. Transcriptional analyses demonstrated that SP cells express genes that encode for stem cell properties like FZD7, HEY1, SMO and ADAM17. Finally she found ADAM17 and FZD7 to be differentially expressed in human gastric cancer, with FZD7- positive intestinal type cancers showing a significant shorter patient survival. In conclusion human gastric cancer cell lines enclose a phenotypically and genotypically distinct cell population with tumor stem cell features. Phenotypical characteristics of this distinct cell population are also present in gastric cancer tissue and seem to correlate with patient survival.

As a first result of our latest projects concerning the role of miRNA in liver regeneration the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology has accepted our paper "Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy": The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small non-coding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in rats under isoflurane anesthesia at different time points (0 hours - 5 days) and after sham laparotomy. Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. 2D-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 hours after resection. The temporal dynamics of liver regeneration were characterized by BrdU, PCNA, IL-6, and HGF. We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 hours after resection. Expression of thirteen miRNAs was significantly reduced 12-48 hours after resection (> 25% change), ouf of which downreguation was confirmed in isolated hepatocytes for 6 miRNAs at 24 hours, whereas three miRNAs were significantly upregulated. Proteomic analysis revealed 65 upregulated proteins; among them 23 represent putative targets of the differentially expressed miRNAs. We provide a temporal miRNA expression and proteomic dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration. Authors are N. Raschzok, W. Werner, H. Sallmon, N. Billecke, C. Dame, P. Neuhaus and I.M. Sauer.