Evaluación del fenotipo de las células madre tumorales de páncreas en la adaptación a la deficiencia de serina y glicina: efectos en la plasticidad metabólica y la evasión inmune

Gordo Ortiz, Andrés
Parejo Alonso, Beatriz (dir.) ; Sancho Andrés, Patricia (dir.)

Moreno Loshuertos, Raquel (ponente)

Universidad de Zaragoza, CIEN, 2024
Departamento de Bioquímica y Biología Molecular y Celular, Área de Bioquímica y Biología Molecular

Graduado en Biotecnología

Resumen: Pancreatic Ductal Adenocarcinoma remains a main cause of cancer-related deaths due to late diagnosis and limited effective treatments. Large regions in pancreatic cancer tissues are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. However, certain cancer cells, such as cancer stem cells (CSCs), can tolerate these severe conditions and survive for prolonged periods. Although many studies have addressed this adaptative behaviour in a myriad of nutrients, not much has been explored for serine and glycine. This work investigates the adaptation mechanisms of pancreatic CSCs to serine and glycine deficiency, focusing on metabolic plasticity and immune evasive properties. This study uses patient-derived xenografts, mRNA quantification, functional flow cytometry and biochemical assays to analyse these changes in their phenotype after deprivation. Key findings indicate an enhanced pluripotency altered immune evasion and reduced triglycerides uptake following deprivation adaptation. Single deprivation of serine or glycine increases overall epithelial-mesenchymal transition (EMT), while double deprivation reduces it, highlighting its complex metabolism. Our results also have implications for understanding the adaptation capabilities and strategies of cancer stem cells in scarce environments.

Tipo de Trabajo Académico: Trabajo Fin de Grado