Endoplasmic reticulum stress response of patient-derived pancreatic ductal adenocarcinoma cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F23%3A00134677" target="_blank" >RIV/00216224:14110/23:00134677 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

čeština

Original language name

Endoplasmic reticulum stress response of patient-derived pancreatic ductal adenocarcinoma cells

Original language description

INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC patients are usually diagnosed with advanced stage of the disease and with poor prognosis due to lack of early biomarkers and insufficient treatments. The epithelial to mesenchymal transition (EMT) has been recognized as a driver of PDAC progression. Also, in recent years, endoplasmic reticulum (ER) stress has been correlated with PDAC. Unfolded protein response (UPR) is the main signaling pathway that is activated by ER overload. We aimed to investigate the ER stress response in patient-derived PDAC cells as a potential target for future therapeutic approaches. METHODS Primary PDAC cell cultures were established from resected tumors of PDAC patients. The ER stress in patient-derived PDAC cells as well as in PANC-1 cell line was induced by tunicamycin treatment for 24 h. The ER stress cellular response was evaluated by immunofluorescence microscopy and western blot analysis. We analyzed the expression levels of two signaling molecules involved in canonical UPR: ER chaperone the binding immunoglobulin protein (BiP) and the C/EBP homologous protein (CHOP). Also, we evaluated the expression levels of epithelial (E-) and neural (N-) cadherins as markers of EMT. To assess the chemical fingerprint of PDAC cells under the ER stress, we applied the intact cell matrix assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS). RESULTS AND CONCLUSION We characterized the UPR in PDAC patient-derived cells and in PANC-1 cell line at basal level and after induction of ER stress. MALDI-TOF MS was shown as a valuable tool for assessment of PDAC heterogeneity with potential of revealing the unique metabolic signature of the PDAC patients. Acknowledgements: This study was supported by AZV ČR (NU23-08-00241) and by Masaryk University (MUNI/A/1301/2022 and MUNI/11/ACC/3/2022)

Czech name

Endoplasmic reticulum stress response of patient-derived pancreatic ductal adenocarcinoma cells

Czech description

INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC patients are usually diagnosed with advanced stage of the disease and with poor prognosis due to lack of early biomarkers and insufficient treatments. The epithelial to mesenchymal transition (EMT) has been recognized as a driver of PDAC progression. Also, in recent years, endoplasmic reticulum (ER) stress has been correlated with PDAC. Unfolded protein response (UPR) is the main signaling pathway that is activated by ER overload. We aimed to investigate the ER stress response in patient-derived PDAC cells as a potential target for future therapeutic approaches. METHODS Primary PDAC cell cultures were established from resected tumors of PDAC patients. The ER stress in patient-derived PDAC cells as well as in PANC-1 cell line was induced by tunicamycin treatment for 24 h. The ER stress cellular response was evaluated by immunofluorescence microscopy and western blot analysis. We analyzed the expression levels of two signaling molecules involved in canonical UPR: ER chaperone the binding immunoglobulin protein (BiP) and the C/EBP homologous protein (CHOP). Also, we evaluated the expression levels of epithelial (E-) and neural (N-) cadherins as markers of EMT. To assess the chemical fingerprint of PDAC cells under the ER stress, we applied the intact cell matrix assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS). RESULTS AND CONCLUSION We characterized the UPR in PDAC patient-derived cells and in PANC-1 cell line at basal level and after induction of ER stress. MALDI-TOF MS was shown as a valuable tool for assessment of PDAC heterogeneity with potential of revealing the unique metabolic signature of the PDAC patients. Acknowledgements: This study was supported by AZV ČR (NU23-08-00241) and by Masaryk University (MUNI/A/1301/2022 and MUNI/11/ACC/3/2022)

Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30400 - Medical biotechnology

Project

<a href="/en/project/NU23-08-00241" target="_blank" >NU23-08-00241: Development of ex-vivo cellular models for pancreatic adenocarcinoma: markers and targets for precision medicine</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů