Evidence map›Paper›PMID 40624709›Full record

ArticleFluids and barriers of the CNS2025

Uptake of DU145 and LNCaP prostate cancer cell line derived extracellular vesicles is inversely correlated with blood-brain barrier integrity in vitro.

Ana Špilak, Adrián Klepe, Sophia Theresa Kriwanek, Heinz-Peter Friedl, Andreas Brachner, Christa Nöhammer, Winfried Neuhaus

Abstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ana Špilak *Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Adrián Klepe *Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Sophia Theresa KriwanekCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Heinz-Peter FriedlCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Andreas BrachnerCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Christa NöhammerCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Winfried NeuhausCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria. winfried.neuhaus@ait.ac.at.

Funding

Austrian Science Fund FWF project P 34137-BEuropean Union's Horizon 2020 research and innovation programme Marie Skłodowska-Curie project No 860303
6 · The paper itself

Abstract

backgroundTumor-derived small extracellular vesicles (sEVs) have been implicated in changes of the blood-brain barrier (BBB) during pre-metastatic niche formation. Although it was postulated that sEVs can traverse the highly restrictive BBB via transcytosis-data mostly based on the indirect detection of transported cargo-direct evidence for sEV transport across the BBB remains elusive due to challenges in sEV labelling, detection limits, and inherent limitations of existing in vitro BBB models. This study investigated the interaction and effects of sEVs derived from low (LNCaP) and moderately metastatic (DU145) prostate cancer (PCa) cell lines with the human brain endothelial cell line hCMEC/D3.

methodsSystematic optimization of the cell culture membrane insert set-up for sEV transport studies was accomplished with inserts with different pore sizes, varied coating procedures and medium compositions. Particle size distribution, quantification and zeta-potential was measured with nanoparticle tracking analysis. Uptake of fluorescent labelled sEVs by hCMEC/D3 cell layers was determined by flow cytometry, barrier integrity was measured by transendothelial electrical resistance (TEER). Effects of inflammatory cytokines and PCa lines-derived sEVs on hCMEC/D3 at the transcriptomic level were investigated by means of high-throughput qPCR based on Fluidigm Biomark® platform.

resultsImproved conditions for sEV transport studies included the application of membrane inserts with 1 µm pore size and of 1% BSA in the receiver compartment. Efficiency of LNCaP- and DU145-derived sEV uptake by hCMEC/D3 cells revealed an inverse correlation between uptake of sEVs and paracellular barrier integrity (TEER). Whereas addition of sEVs of the more aggressive DU145 cells resulted in a distinct increase of TEER under regular and inflammatory conditions, LNCaP-derived sEVs affected TEER only upon inflammatory cytokine treatment. MRNA expression analyses of hCMEC/D3 cells revealed a distinct regulation of transcripts depending on TEER (i.a. FN, CDLN1) or upon inflammatory cytokines (i.a.: ABCB1, MFSD2a, VCAM1, VEGFa).

conclusionsDifferences upon treatment of hCMEC/D3 layers with LNCaP-and DU145 derived sEVs indicated that vesicles retain and transport molecular features of their originating cells. Careful optimization of the test set-up for studies with sEVs in vitro is recommended, including medium controls for sEV purification and labelling as well as addition of proteins for sEV recovery.

Indexed as

Blood-Brain BarrierEndothelial CellsExtracellular VesiclesProstatic NeoplasmsCell Line, TumorHumansMaleBiological barriersBlood–brain barrierInflammatory cytokinesProstate cancerSmall extracellular vesicles

Identifiers

PMID40624709
PMCPMC12232752

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.