Investigating the Impact of Microgravity on Cancer Cell Behavior and Drug Response: Implications for Novel Therapeutic Strategies

This PhD thesis investigates the profound impact of simulated microgravity (SMG) on both cancerous and non-cancerous cellular behavior and their drug responses. Specifically, this thesis examines cancer induction in pleura mesothelial cells and SMG-induced alterations in pancreatic ductal adenocarcinoma (PDAC) cells, highlighting Trichostatin A's (TSA) potential to restore normal cellular phenotypes. Ultimately, this work highlights simulated microgravity as an exciting new avenue for cancer biology and for developing advanced 3D cell culture models. Further insights reveal that SMG induces a tumoral switch in mesothelial cells by altering cytoskeleton and adhesion proteins (actin, vinculin, connexin-43). SMG exposure leads to expression patterns of tumoral markers (p27, CD44, Fibulin-3, NANOG) and cancer-related genes (NANOG, CDH-1, Zeb-1) resembling malignant cells. In PDAC cell line, the research work details the molecular and proteomic effects of TSA treatment under SMG. This treatment significantly impacts cell growth, modulates cytokeratin, and influences proteins involved in apoptosis, metabolism, and synthesis. It impairs the cell cycle (Cdc42, G1/G2-, G2/M-phase transitions), and modifies survival, autophagy, transcription regulation, and DNA repair pathways. Crucially, TSA downregulates stem cell potency markers while upregulating differentiation-inducing proteins. These findings suggest TSA's capability to restore the cellular phenotype, reduce proliferation, and induce cell death, offering a promising therapeutic direction.