Evidence map›Paper›PMID 27598125›Full record

ArticleInternational journal of molecular sciences2016

Cancer-Associated Fibroblasts Modify the Response of Prostate Cancer Cells to Androgen and Anti-Androgens in Three-Dimensional Spheroid Culture.

Theresa Eder, Anja Weber, Hannes Neuwirt, Georg Grünbacher, Christian Ploner, Helmut Klocker, Natalie Sampson, Iris E Eder

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

51 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
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  4. Review
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  8. Article
  9. Article
  10. Article
  11. Article
  12. Prostate Cancer and the Mevalonate Pathway.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. 3D Tumor Models in Urology.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Review
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

8 authors at 1 institution in 2 countries.

Theresa EderDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. theresa.eder@charite.de.
Anja WeberDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. anja.weber@i-med.ac.at.
Hannes NeuwirtDepartment of Internal Medicine IV-Nephrology and Hypertension, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. hannes.neuwirt@i-med.ac.at.
Georg GrünbacherDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. georg.gruenbacher@gmail.com.
Christian PlonerDepartment of Plastic, Reconstructive & Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. christian.ploner@tirol-kliniken.at.
Helmut KlockerDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. helmut.klocker@tirol-kliniken.at.
Natalie SampsonDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. natalie.sampson@i-med.ac.at.
Iris E EderDivision of Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. iris.eder@i-med.ac.at.
Innsbruck Medical University · AT

Funding

Austrian Science Fund FWF V 216
6 · The paper itself

Abstract

Androgen receptor (AR) targeting remains the gold standard treatment for advanced prostate cancer (PCa); however, treatment resistance remains a major clinical problem. To study the therapeutic effects of clinically used anti-androgens we characterized herein a tissue-mimetic three-dimensional (3D) in vitro model whereby PCa cells were cultured alone or with PCa-associated fibroblasts (CAFs). Notably, the ratio of PCa cells to CAFs significantly increased in time in favor of the tumor cells within the spheroids strongly mimicking PCa in vivo. Despite this loss of CAFs, the stromal cells, which were not sensitive to androgen and even stimulated by the anti-androgens, significantly influenced the sensitivity of PCa cells to androgen and to the anti-androgens bicalutamide and enzalutamide. In particular, DuCaP cells lost sensitivity to enzalutamide when co-cultured with CAFs. In LAPC4/CAF and LNCaP/CAF co-culture spheroids the impact of the CAFs was less pronounced. In addition, 3D spheroids exhibited a significant increase in E-cadherin and substantial expression of vimentin in co-culture spheroids, whereas AR levels remained unchanged or even decreased. In LNCaP/CAF spheroids we further found increased Akt signaling that could be inhibited by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002, thereby overcoming the anti-androgen resistance of the spheroids. Our data show that CAFs influence drug response of PCa cells with varying impact and further suggest this spheroid model is a valuable in vitro drug testing tool.

Indexed as

Androgen AntagonistsAndrogensBenzamidesCadherinsCell Line, TumorCoculture TechniquesEpithelial CellsFibroblastsHumansMaleNitrilesPhenylthiohydantoinPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProstatic NeoplasmsProto-Oncogene Proteins c-aktAndrogen AntagonistsAndrogensBenzamidesCadherinsenzalutamideNitrilesPhenylthiohydantoinPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktVimentinAkt signalinganti-androgenscancer-associated fibroblastsE-cadherinprostate cancerthree-dimensional epithelial–stromal spheroids

Identifiers

PMID27598125
PMCPMC5037737
OpenAlexW2514594897

What OpenQuestion 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 OpenQuestion graph.