Evidence map›Paper›PMID 24663399›Full record

ArticlePloS one2014

Development of an innovative 3D cell culture system to study tumour--stroma interactions in non-small cell lung cancer cells.

Arno Amann, Marit Zwierzina, Gabriele Gamerith, Mario Bitsche, Julia M Huber, Georg F Vogel, Michael Blumer, Stefan Koeck, Elisabeth J Pechriggl, Jens M Kelm and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 164 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. 3D cancer models: One step closer toFrontiers in immunology · 2023
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. 3D Cell Culture Systems: Tumor Application, Advantages, and Disadvantages.International journal of molecular sciences · 2021
    Review
  20. Review

14 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Arno AmannDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Marit ZwierzinaDepartment of Anatomy, Histology and Embryology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Gabriele GamerithDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Mario BitscheDepartment of Anatomy, Histology and Embryology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Julia M HuberDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Georg F VogelDepartment of Anatomy, Histology and Embryology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Michael BlumerDepartment of Anatomy, Histology and Embryology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Stefan KoeckDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Elisabeth J PechrigglDepartment of Anatomy, Histology and Embryology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Jens M KelmInSphero AG, Schlieren, Canton of Zürich, Switzerland.
Wolfgang HilbeDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Heinz ZwierzinaDepartment of Internal Medicine V, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
Innsbruck Medical University · ATInspire · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionWe describe a novel 3D co-culture model using non-small cell lung cancer (NSCLC) cell lines in combination with lung fibroblasts. This model allows the investigation of tumour-stroma interactions and addresses the importance of having a more in vivo like cell culture model.

methodsAutomation-compatible multi-well hanging drop microtiter plates were used for the production of 3D mono- and co-cultures. In these hanging drops the two NSCLC cell lines A549 and Colo699 were cultivated either alone or co-cultured with lung fibroblasts. The viability of tumour spheroids was confirmed after five and ten days by using Annexin V/Propidium Iodide staining for flow-cytometry. Tumour fibroblast spheroid formation was characterized by scanning electron microscope (SEM), semi-thin sections, fluorescence microscope and immunohistochemistry (IHC). In addition to conventional histology, protein expression of E-Cadherin, vimentin, Ki67, fibronectin, cytokeratin 7 and α-smooth muscle actin (α-SMA) was investigated by IHC.

resultsLower viability was observed in A549 monocultures compared to co-cultures, whereas Colo699 monocultures showed better viability compared to co-cultures. Ki67 expression varied significantly between mono- and co-cultures in both tumour cell lines. An increase of vimentin and decreased E-Cadherin expression could be detected during the course of the cultivation suggesting a transition to a more mesenchymal phenotype. Furthermore, the fibroblast cell line showed an expression of α-SMA only in co-culture with the cancer cell line A549, thereby indicating a mesenchymal to mesenchymal shift to an even more myofibroblast phenotype.

conclusionWe demonstrate that our method is a promising tool for the generation of tumour spheroid co-cultures. Furthermore, these spheroids allow the investigation of tumour-stroma interactions and a better reflection of in vivo conditions of cancer cells in their microenvironment. Our method holds potential to contribute to the development of anti-cancer agents and support the search for biomarkers.

Indexed as

Cell CommunicationCarcinoma, Non-Small-Cell LungCell Culture TechniquesCell Line, TumorCell ProliferationCoculture TechniquesDrug DiscoveryFibroblastsGene Expression Regulation, NeoplasticHumansLung NeoplasmsStromal Cells

Identifiers

PMID24663399
PMCPMC3963897
OpenAlexW1964129215

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.