Metabolism of primary high-grade serous ovarian carcinoma
(HGSOC) cells under limited glutamine or glucose availability

J 2024

Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability

SIMCIKOVA, Daniela; Dominik GARDAS; Tomas PELIKAN; Lukáš MORÁŇ; Martin HRUDA et al.

Základní údaje

Originální název

Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability

Autoři

SIMCIKOVA, Daniela; Dominik GARDAS; Tomas PELIKAN; Lukáš MORÁŇ; Martin HRUDA; Katerina HLOZKOVA; Tiziana PIVETTA; Michal HENDRYCH; Julia STARKOVA; Lukas ROB; Petr VAŇHARA a Petr HENEBERG

Vydání

CANCER & METABOLISM, LONDON, BMC, 2024, 2049-3002

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.300

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00137171

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1186/s40170-024-00355-1

UT WoS

001314036200001

Klíčová slova anglicky

Epithelial ovarian carcinoma; Metabolism reprogramming; Ovarian fibroblasts; Oxidative phosphorylation; Patient-derived cells; Unfolded protein response

Štítky

14110112, 14110517, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 10. 2024 09:53, Mgr. Tereza Miškechová

Anotace

V originále

BackgroundHigh-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal.MethodsWe isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism.ResultsThe primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts.ConclusionsAnalysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

MUNI/A/1598/2023, interní kód MU

Název: Zdroje pro tkáňové inženýrství 14

Investor: Masarykova univerzita, Zdroje pro tkáňové inženýrství 14

NU21-03-00539, projekt VaV

Název: Vliv stresu endoplazmatického retikula na imunitní stav nádorů a účinnost imunoterapie při léčbě ovariálního a renálního karcinomu

Investor: Ministerstvo zdravotnictví ČR, Vliv stresu endoplazmatického retikula na imunitní stav nádorů a účinnost imunoterapie při léčbě ovariálního a renálního karcinomu, Podprogram 1 - standardní

Přiložené soubory

Metabolism_of_primary_high-grade_serous_ovarian_carcinoma__HGSOC__cells_under_limited_glutamine_or_glucose_availability.pdf

Citovat

SIMCIKOVA, Daniela; Dominik GARDAS; Tomas PELIKAN; Lukáš MORÁŇ; Martin HRUDA; Katerina HLOZKOVA; Tiziana PIVETTA; Michal HENDRYCH; Julia STARKOVA; Lukas ROB; Petr VAŇHARA a Petr HENEBERG. Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability. CANCER & METABOLISM. LONDON: BMC, 2024, roč. 12, č. 1, s. 1-19. ISSN 2049-3002. Dostupné z: https://doi.org/10.1186/s40170-024-00355-1.

@article{2435858,
   author = {Simcikova, Daniela and Gardas, Dominik and Pelikan, Tomas and Moráň, Lukáš and Hruda, Martin and Hlozkova, Katerina and Pivetta, Tiziana and Hendrych, Michal and Starkova, Julia and Rob, Lukas and Vaňhara, Petr and Heneberg, Petr},
   article_location = {LONDON},
   article_number = {1},
   doi = {https://doi.org/10.1186/s40170-024-00355-1},
   keywords = {Epithelial ovarian carcinoma; Metabolism reprogramming; Ovarian fibroblasts; Oxidative phosphorylation; Patient-derived cells; Unfolded protein response},
   language = {eng},
   issn = {2049-3002},
   journal = {CANCER & METABOLISM},
   title = {Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability},
   url = {https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-024-00355-1},
   volume = {12},
   year = {2024}
}

TY  - JOUR
ID  - 2435858
AU  - Simcikova, Daniela - Gardas, Dominik - Pelikan, Tomas - Moráň, Lukáš - Hruda, Martin - Hlozkova, Katerina - Pivetta, Tiziana - Hendrych, Michal - Starkova, Julia - Rob, Lukas - Vaňhara, Petr - Heneberg, Petr
PY  - 2024
TI  - Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability
JF  - CANCER & METABOLISM
VL  - 12
IS  - 1
SP  - 1-19
EP  - 1-19
PB  - BMC
SN  - 20493002
KW  - Epithelial ovarian carcinoma
KW  - Metabolism reprogramming
KW  - Ovarian fibroblasts
KW  - Oxidative phosphorylation
KW  - Patient-derived cells
KW  - Unfolded protein response
UR  - https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-024-00355-1
N2  - BackgroundHigh-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal.MethodsWe isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism.ResultsThe primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts.ConclusionsAnalysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels.
ER  -

SIMCIKOVA, Daniela; Dominik GARDAS; Tomas PELIKAN; Lukáš MORÁŇ; Martin HRUDA; Katerina HLOZKOVA; Tiziana PIVETTA; Michal HENDRYCH; Julia STARKOVA; Lukas ROB; Petr VAŇHARA a Petr HENEBERG. Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability. \textit{CANCER \&{} METABOLISM}. LONDON: BMC, 2024, roč.~12, č.~1, s.~1-19. ISSN~2049-3002. Dostupné z: https://doi.org/10.1186/s40170-024-00355-1.

Přehled o publikaci