<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma"^^ . "Pancreatic ductal adenocarcinoma (PDAC) stands as a formidable challenge in \r\noncology due to its high mortality rate (5-year survival < 11%1\r\n) and neurotropic characteristics.\r\nThe presence of hypertrophied nerves and neural invasion in virtually all patients correlates \r\nwith worsened prognosis and severe pain. \r\nWhile tumour-nerve interactions and cancer metabolism are two prominent emerging \r\nfields, only few studies so far have set to understand how nerves can sustain or reprogram \r\ncancer metabolism. This study unravels the nerve-triggered metabolic reprogramming of \r\nPDAC cancer cells using spatial metabolomics at near single-cell level. Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP) – key sensory neurotransmitters – increased \r\ntriglycerides storage while glutamate – the most abundant excitatory neurotransmitter –\r\npromoted γ-glutamyl amino acid synthesis and downregulation of glutathione synthesis \r\npathway. I developed a protocol for co-culture of cancer cells and primary neurons compatible \r\nwith a state-of-the-art technology of spatial near single-cell metabolomics and could validate \r\nthe γ-glutamyl amino acid-related findings, suggesting that cancer cells are able to use \r\nneurotransmitters for their own metabolism, and found other small molecule markers expressed \r\nonly by cancer cells in presence with neurons. While spatial metabolomics was for a long time \r\nonly used for tissue imaging, I show here the relevance of this tool to address complex \r\nmechanistic questions in advanced and pharmacologically relevant co-culture systems at the \r\nnear single-cell level. This research shows the importance of spatial metabolomics towards \r\nunderstanding PDAC's neurotropism, paving the way for targeted therapies that disrupt nerve-driven metabolic reprogramming in cancer cells, alleviate patient suffering, and improve \r\nclinical outcomes.\r\nThe structural changes of nerves within the tumour environment and their role in PDAC \r\nand pain management are unknown. Here, I showed that nerves in PDAC patients present \r\nunique ultrastructural features resembling nerve injury and defective repair mechanisms using\r\ntargeted Correlative Light and Electron Microscopy (t-CLEM). I found that PDAC nerves\r\ncontained less myelinated axons but more and smaller unmyelinated axons that presented\r\nbundling defects per Remak Schwann cell. Finally, this study provided the first high resolution \r\ncharacterisation of cancer cells invading nerves in PDAC patient tissue. These results open \r\navenues for new perspectives on approaching neural alterations in PDAC, improving pain and \r\nquality of life management in patients, and further understanding neural plasticity."^^ . "2026" . . . . . . . "Amandine"^^ . "Prats"^^ . "Amandine Prats"^^ . . . . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (PDF)"^^ . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (Other)"^^ . . . . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (Other)"^^ . . . . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (Other)"^^ . . . . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (Other)"^^ . . . . . . "Metabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma (Other)"^^ . . . . . "HTML Summary of #36447 \n\nMetabolomic and structural characterisation of tumour-nerve interaction in pancreatic ductal adenocarcinoma\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .