Genome-wide microarray analysis revealed three major phenotypic changes in fibroblast spheroids compared to standard BIRB 796 nmr 2-dimensional culture; arrest in cell cycle, downregulation of cytoskeleton and induction of secreted proteins (chemokines, proinflammatory cytokines and
growth factors). In addition to downregulation of cell cycle proteins, the list of upregulated genes resembled remarkably those reported to be induced during cellular senescence. Furthermore, fibroblast spheroids stained positively to senescence associated ß-galactosidase. Interestingly, classical senescence pathways, p53-p21 and retinoblastoma, were downregulated. Furthermore, the cell cycle arrest was reversible, indicating a mechanism different from that in cellular senescence. A mechanism to leading to this activation CUDC-907 manufacturer (now named as nemosis) and cell cycle arrest is still largely uncharacterized, but one of the first processes seen in nemosis is autophagy. Keeping in mind the important role of autophagy in cellular senescence, it might be that autophagy has a major role in regulation this kind of fibroblast SGC-CBP30 solubility dmso activation. Since senescent fibroblasts have been shown to stimulate growth of non-invasive cells in vivo and convert them to invasive, we tested whether fibroblast spheroids
are able to modulate growth of metastatic keratinocytes in xenograft model. Interestingly, fibroblast spheroids were able to inhibit growth of tumor cells in vivo. Our results show an important and interesting function of fibroblasts. Furthermore, targeting mechanisms leading to nemotic activation may function as a new therapeutic approach in cancer treatment. This work was supported by the Helsinki Graduate School in Biotechnology and Molecular Biology, Finnish Cancer Societies, and Academy of Finland. Poster No. 49 Inhibitory Effects of Tumor-derived 5′- Deoxy- 5′-Methylthioadenosine (MTA) on Human T Cells Katrin Pregnenolone Singer 1
, Axel Stevens2, Christine Hammerschmied3, Michael Aigner1, Katja Dettmer2, Anja Bosserhoff4, Peter Oefner2, Marina Kreutz5, Arndt Hartmann3, Andreas Mackensen1 1 Department of Internal Medicine 5, Haematology/Oncology, University of Erlangen, Erlangen, Germany, 2 Institute of Functional Genomics, University of Regensburg, Regensburg, Germany, 3 Institute of Pathology, University of Erlangen, Erlangen, Germany, 4 Institute of Pathology, University of Regensburg, Regensburg, Germany, 5 Department of Haematology/Oncology, University of Regensburg, Regensburg, Germany Tumor cells develop multiple mechanisms including a dysregulated metabolism to escape T-cell mediated immune recognition. Tumor-derived metabolites are known to modulate cellular components of stromal cells, like immune effector cells and antigen-presenting cells.