Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors
Menée à l'aide de lignées cellulaires d'adénocarcinome canalaire du pancréas, d'organoïdes et de modèles murins, cette étude met en évidence un mécanisme par lequel les cellules cancéreuses, en interagissant directement avec les cellules étoilées du pancréas, peuvent lever les contraintes imposées par les réactions d'oxydo-réduction pour mieux proliférer
Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Nontransformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide cofactors we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells. This suggests that metabolic interaction between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.
Science Advances 2022