PMID- 34249925
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210713
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Wnt Activity and Cell Proliferation Are Coupled to Extracellular Vesicle Release 
      in Multiple Organoid Models.
PG  - 670825
LID - 10.3389/fcell.2021.670825 [doi]
LID - 670825
AB  - Extracellular vesicles (EV) are considered as a potential tool for early disease 
      diagnosis; however, factors modifying EV release remain partially unknown. By 
      using patient-derived organoids that capture the cellular heterogeneity of 
      epithelial tissues, here we studied the connection between the Wnt-producing 
      microniche and EV secretion in multiple tissues. Although nearly all cells in 
      pancreatic ductal (PD) and pancreatic ductal adenocarcinoma (PDAC) samples 
      expressed porcupine (PORCN), an enzyme critical for Wnt secretion, only a 
      subpopulation of lung bronchiolar (NL) and lung adenocarcinoma (LUAD) organoid 
      cells produced active Wnt. The microniche for proliferating cells was shaped not 
      only by PORCN + cells in NL and LUAD organoids but also by fibroblast-derived 
      EVs. This effect could be blocked by using Wnt secretion inhibitors. Whereas 
      inhibiting Wnt secretion in PD NL or LUAD organoids critically changed both cell 
      proliferation and EV release, these were uncoupled from each other in PDAC. 
      Sorting for CD133 identified a cell population in the LUAD microniche that 
      produced organoids with a high percentage of PORCN + and proliferating cells and 
      an elevated EV secretion, which may explain that CD133 marks LUAD cells with 
      malignant behavior. Collectively, we show here that high cell proliferation rate, 
      induced by Wnt pathway activation, is coupled to a higher EV release, a critical 
      finding that may be considered when developing EV-based diagnostic tools.
CI  - Copyright (c) 2021 Sandor, Soos, Lorincz, Rojko, Harko, Bogyo, Tolgyes, Bursics, 
      Buzas, Moldvay and Wiener.
FAU - Sandor, Gyongyver Orsolya
AU  - Sandor GO
AD  - Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
FAU - Soos, Andras Aron
AU  - Soos AA
AD  - Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
FAU - Lorincz, Peter
AU  - Lorincz P
AD  - Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University 
      of Sciences, Budapest, Hungary.
AD  - Premium Postdoctoral Research Program, Hungarian Academy of Sciences, Budapest, 
      Hungary.
FAU - Rojko, Livia
AU  - Rojko L
AD  - 1st Department of Pulmonology, National Koranyi Institute of Pulmonology, 
      Budapest, Hungary.
FAU - Harko, Tunde
AU  - Harko T
AD  - Department of Pathology, National Koranyi Institute of Pulmonology, Budapest, 
      Hungary.
FAU - Bogyo, Levente
AU  - Bogyo L
AD  - Department of Thoracic Surgery, Semmelweis University and National Institute of 
      Oncology, Budapest, Hungary.
AD  - Department of Thoracic Surgery, National Koranyi Institute of Pulmonology, 
      Budapest, Hungary.
FAU - Tolgyes, Tamas
AU  - Tolgyes T
AD  - Department of General Surgery and Surgical Oncology, Uzsoki Hospital, Budapest, 
      Hungary.
FAU - Bursics, Attila
AU  - Bursics A
AD  - Department of General Surgery and Surgical Oncology, Uzsoki Hospital, Budapest, 
      Hungary.
FAU - Buzas, Edit I
AU  - Buzas EI
AD  - Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
AD  - ELKH-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Semmelweis 
      University, Budapest, Hungary.
AD  - HCEMM-SE Extracellular Vesicle Research Group, Budapest, Hungary.
FAU - Moldvay, Judit
AU  - Moldvay J
AD  - 1st Department of Pulmonology, National Koranyi Institute of Pulmonology, 
      Budapest, Hungary.
AD  - SE-NAP Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis 
      University, Budapest, Hungary.
FAU - Wiener, Zoltan
AU  - Wiener Z
AD  - Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
LA  - eng
PT  - Journal Article
DEP - 20210624
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8264557
OTO - NOTNLM
OT  - CD133
OT  - exosome
OT  - lung adenocarcinoma
OT  - lung cancer
OT  - organoid
OT  - pancreatic ductal adenocarcinoma
OT  - prominin-1
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/13 06:00
MHDA- 2021/07/13 06:01
PMCR- 2021/01/01
CRDT- 2021/07/12 05:57
PHST- 2021/02/22 00:00 [received]
PHST- 2021/05/27 00:00 [accepted]
PHST- 2021/07/12 05:57 [entrez]
PHST- 2021/07/13 06:00 [pubmed]
PHST- 2021/07/13 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.670825 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Jun 24;9:670825. doi: 10.3389/fcell.2021.670825. 
      eCollection 2021.