J 2023

Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles

HÁNĚLOVÁ, Klára, Martina RAUDENSKÁ, Monika KRATOCHVÍLOVÁ, Jiří NAVRÁTIL, Tomáš VIČAR et. al.

Basic information

Original name

Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles

Authors

HÁNĚLOVÁ, Klára (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Monika KRATOCHVÍLOVÁ (203 Czech Republic, belonging to the institution), Jiří NAVRÁTIL (203 Czech Republic, belonging to the institution), Tomáš VIČAR (203 Czech Republic, belonging to the institution), Mária BUGAJOVÁ (703 Slovakia, belonging to the institution), Jaromír GUMULEC (203 Czech Republic, belonging to the institution), Michal MASAŘÍK (203 Czech Republic, belonging to the institution) and Jan BALVAN (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cell Communication and Signaling, LONDON, BMC, 2023, 1478-811X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 8.400 in 2022

RIV identification code

RIV/00216224:14110/23:00131018

Organization unit

Faculty of Medicine

DOI

UT WoS

000994734500001

Keywords in English

Extracellular vesicles

Tags

Tags

International impact, Reviewed
Změněno: 8/4/2024 10:08, Mgr. Tereza Miškechová

Abstract

V originále

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators.

Links

EF18_046/0015974, research and development project
Name: Modernizace České infrastruktury pro integrativní strukturní biologii
GA21-06873S, research and development project
Name: Metabolická symbióza mezi nádorovými buňkami a fibroblasty asociovaných s nádorem u nádorů v oblasti hlavy a krku
Investor: Czech Science Foundation
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
LM2018140, research and development project
Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)
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/1343/2022, interní kód MU
Name: Zátěže kardiovaskulárního systému od A po Z
Investor: Masaryk University, Loads on the cardiovascular system from A to Z
MUNI/A/1370/2022, 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
NU20J-08-00018, research and development project
Name: Exosomální RNA produkovaná fibroblasty asociovanými s nádorem jako relevantní marker v prognóze nádorů hlavy a krku
Investor: Ministry of Health of the CR, Subprogram 2 - junior
NU22-03-00202, research and development project
Name: Proteom extracelulárních vezikul - neprozkoumaná oblast mezibuněčné komunikace v mikroprostředí nádorů hlavy a krku
Investor: Ministry of Health of the CR, Subprogram 1 - standard
90242, large research infrastructures
Name: CIISB III
90250, large research infrastructures
Name: Czech-BioImaging III