a 2023

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

AĆIMOVIĆ, Ivana, Viktorie GABRIELOVÁ, Riza Can CAKMAKCI, Lukáš PEČINKA, Lukáš MORÁŇ et. al.

Základní údaje

Originální název

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

Název anglicky

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

Autoři

AĆIMOVIĆ, Ivana (688 Srbsko, domácí), Viktorie GABRIELOVÁ (203 Česká republika, domácí), Riza Can CAKMAKCI (792 Turecko, domácí), Lukáš PEČINKA (203 Česká republika, domácí), Lukáš MORÁŇ (203 Česká republika, domácí), Martina VODINSKÁ (203 Česká republika, domácí), Vendula PELKOVÁ (203 Česká republika, domácí), Michal EID (203 Česká republika, domácí), Petr MORAVČÍK (203 Česká republika, domácí), Jakub VLAŽNÝ (203 Česká republika, domácí), Zdeněk KALA (203 Česká republika, domácí) a Petr VAŇHARA (203 Česká republika, garant, domácí)

Vydání

BIOCEV Regeneration III, 2023

Další údaje

Jazyk

čeština

Typ výsledku

Konferenční abstrakt

Obor

30400 3.4 Medical biotechnology

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14110/23:00134677

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

PDAC; endoplasmic reticulum; unfolded protein response; mass spectrometry
Změněno: 24. 11. 2023 07:52, doc. RNDr. Petr Vaňhara, Ph.D.

Anotace

V originále

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)

Anglicky

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)

Návaznosti

MUNI/A/1301/2022, interní kód MU
Název: Zdroje pro tkáňové inženýrství 13
Investor: Masarykova univerzita, Zdroje pro tkáňové inženýrství 13
MUNI/11/ACC/3/2022, interní kód MU
Název: Bioanalytical quality control of cGMP/ATMP-grade stem cells and progenitors
Investor: Masarykova univerzita, Bioanalytical quality control of cGMP/ATMP-grade stem cells and progenitors, Accelerate
NU23-08-00241, projekt VaV
Název: Vývoj ex-vivo buněčných modelů pro adenokarcinom pankreatu: markery a cíle pro precizní medicínu
Investor: Ministerstvo zdravotnictví ČR, Vývoj ex-vivo buněčných modelů pro adenokarcinom pankreatu: markery a cíle pro precizní medicínu, Podprogram 1 - standardní