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.

Basic information

Original name

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

Name (in English)

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

Authors

AĆIMOVIĆ, Ivana (688 Serbia, belonging to the institution), Viktorie GABRIELOVÁ (203 Czech Republic, belonging to the institution), Riza Can CAKMAKCI (792 Turkey, belonging to the institution), Lukáš PEČINKA (203 Czech Republic, belonging to the institution), Lukáš MORÁŇ (203 Czech Republic, belonging to the institution), Martina VODINSKÁ (203 Czech Republic, belonging to the institution), Vendula PELKOVÁ (203 Czech Republic, belonging to the institution), Michal EID (203 Czech Republic, belonging to the institution), Petr MORAVČÍK (203 Czech Republic, belonging to the institution), Jakub VLAŽNÝ (203 Czech Republic, belonging to the institution), Zdeněk KALA (203 Czech Republic, belonging to the institution) and Petr VAŇHARA (203 Czech Republic, guarantor, belonging to the institution)

Edition

BIOCEV Regeneration III, 2023

Other information

Language

Czech

Type of outcome

Konferenční abstrakt

Field of Study

30400 3.4 Medical biotechnology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14110/23:00134677

Organization unit

Faculty of Medicine

Keywords in English

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

Abstract

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)

In English

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)

Links

MUNI/A/1301/2022, interní kód MU
Name: Zdroje pro tkáňové inženýrství 13
Investor: Masaryk University
MUNI/11/ACC/3/2022, interní kód MU
Name: Bioanalytical quality control of cGMP/ATMP-grade stem cells and progenitors
Investor: Masaryk University, Accelerate
NU23-08-00241, research and development project
Name: Vývoj ex-vivo buněčných modelů pro adenokarcinom pankreatu: markery a cíle pro precizní medicínu
Investor: Ministry of Health of the CR, Development of ex vivo cellular models for pancreatic adenocarcinoma: markers and targets for precision medicine, Subprogram 1 - standard