J 2024

Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells

NAVRÁTIL, Jiří, Monika KRATOCHVÍLOVÁ, Martina RAUDENSKÁ, Jan BALVAN, Tomáš VIČAR et. al.

Basic information

Original name

Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells

Authors

NAVRÁTIL, Jiří (203 Czech Republic, belonging to the institution), Monika KRATOCHVÍLOVÁ (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution), Tomáš VIČAR (203 Czech Republic, belonging to the institution), Kateřina PETRLÁKOVÁ (203 Czech Republic, belonging to the institution), Kanako SUZUKI (392 Japan, belonging to the institution), Lucie JADRNA (203 Czech Republic), Jiri BURSA (203 Czech Republic), Martin KRÄTER (276 Germany), Kyoohyun KIM (276 Germany), Michal MASAŘÍK (203 Czech Republic, belonging to the institution) and Jaromír GUMULEC (203 Czech Republic, belonging to the institution)

Edition

Cancer Cell International, London, BMC, 2024, 1475-2867

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.800 in 2022

Organization unit

Faculty of Medicine

UT WoS

001310159400002

Keywords in English

Mechanobiology; Zinc; Actin; Cytoskeleton; Mitochondria; Vimentin; Metabolism; Cancer

Tags

International impact, Reviewed
Změněno: 23/9/2024 13:01, Mgr. Tereza Miškechová

Abstract

V originále

The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.

Links

EF18_046/0015974, research and development project
Name: Modernizace České infrastruktury pro integrativní strukturní biologii
LM2018129, research and development project
Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging
Investor: Ministry of Education, Youth and Sports of the CR
LM2023042, research and development project
Name: Česká infrastruktura pro integrativní strukturní biologii
Investor: Ministry of Education, Youth and Sports of the CR, CIISB - Czech Infrastructure for Integrative Structural Biology
MUNI/A/1587/2023, interní kód MU
Name: Patofyziologie vybraných komplexních nemocí od molekulární do systémovou úroveň
Investor: Masaryk University, Pathophysiology of selected complex diseases from molecular to systemic level
NU22J-08-00062, research and development project
Name: Mechanická a morfologická high-throughput fenotypizace nádorových buněk během smykového napětí: prediktor migračního a invazivního potenciálu
Investor: Ministry of Health of the CR, Subprogram 2 - junior
90254, large research infrastructures
Name: e-INFRA CZ II
964997, interní kód MU
Name: Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe (Acronym: A4L_ACTIONS)
Investor: European Union, Health, demographic change and wellbeing (Societal Challenges)