Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level

• DOI: 10.1002/1878-0261.13282
• Publication Date: 2022-07-11T07:31:10Z
• Authors: Margaretha A. Sko...; Katharina Eul; Alexa Stephan; Gillian F. Ludwig; Gamal A. Wakileh; Arthur Bister; Christian Söhngen; Katharina Raba; Patrick Petzsch; Gereon Poschmann; Edmund Osei Kuffour; Daniel Degrandi; Shafaqat Ali; Constanze Wiek; Helmut Hanenberg; Carsten Münk; Kai Stühler; Karl Köhrer; Elvira Mass; Daniel Nettersheim
• Keywords: Profiling (computer programming)

The tumor microenvironment (TM), consisting of the extracellular matrix (ECM), fibroblasts, endothelial cells, and immune might affect invasiveness outcome standard chemotherapy. This study investigated cross talk between germ cell tumors (GCT) surrounding TM cells (macrophages, T-lymphocytes, fibroblasts) at transcriptome secretome level. Using high-throughput approaches three-dimensional (3D) co-cultured cellular aggregates, this offers newly identified pathways to be studied with regard sensitivity toward cisplatin-based chemotherapy or as a consequence components. Mass-spectrometry-based analyses revealed that secreted factors involved in ECM organization, adhesion, angiogenesis, regulation insulin-like growth factor (IGF) transport. To evaluate direct cell-cell contacts, green fluorescent protein (GFP)-expressing GCT mCherry-expressing were 3D. Afterward, populations separated by flow cytometry analyzed RNA sequencing. Correlating data indicated molecular processes such adhesion components being enriched most populations. Re-analyses lysine- proline-hydroxylated peptides gain proteins, collagens fibronectin. Cultivation on collagen I/IV- fibronectin-coated plates significantly elevated adhesive migratory capacity, while decreasing cisplatin cells. Correspondingly, was reduced under influence conditioned medium from fibroblasts sheds light their circumjacent TM, which results deposition eventually promotes pro-tumorigenic environment through enhanced well decreased sensitivity. Hence, our observations indicate targeting its novel therapeutic option combination for patients.