Evidence map›Paper›PMID 26375443›Full record

ArticleOncotarget2015

Automated tracking of tumor-stroma morphology in microtissues identifies functional targets within the tumor microenvironment for therapeutic intervention.

Malin Åkerfelt, Neslihan Bayramoglu, Sean Robinson, Mervi Toriseva, Hannu-Pekka Schukov, Ville Härmä, Johannes Virtanen, Raija Sormunen, Mika Kaakinen, Juho Kannala and 3 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Consistent Inclusion of Mesenchymal Stem Cells into In Vitro Tumor Models.Methods in molecular biology (Clifton, N.J.) · 2021
    Review
  12. In Vitro Modeling of the Tumor Microenvironment in Tumor Organoids.Tissue engineering and regenerative medicine · 2020
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

13 authors at 5 institutions in 2 countries.

Malin ÅkerfeltTurku Centre for Biotechnology, University of Turku, Turku, FI-20520, Finland.
Neslihan BayramogluCentre for Machine Vision Research, University of Oulu, Oulu, FI-90014, Finland.
Sean RobinsonDepartment of Mathematics and Statistics, University of Turku, Turku, FI-20014, Finland.
Mervi TorisevaTurku Centre for Biotechnology, University of Turku, Turku, FI-20520, Finland.
Hannu-Pekka SchukovInstitute of Biomedicine, University of Turku, Turku, FI-20520, Finland.
Ville HärmäVTT Technical Research Centre of Finland, Turku, FI-20521, Finland.
Johannes VirtanenVTT Technical Research Centre of Finland, Turku, FI-20521, Finland.
Raija SormunenBiocenter Oulu and Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, FI-90220, Finland.
Mika KaakinenOulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, FI-90014, Finland.
Juho KannalaCentre for Machine Vision Research, University of Oulu, Oulu, FI-90014, Finland.
Lauri EklundOulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, FI-90014, Finland.
Janne HeikkiläCentre for Machine Vision Research, University of Oulu, Oulu, FI-90014, Finland.
Matthias NeesTurku Centre for Biotechnology, University of Turku, Turku, FI-20520, Finland.
University of Oulu · FIVTT Technical Research Centre of Finland · FITurku Centre for Biotechnology · FIUniversity of Turku · FIOulu University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of complex cell cultures has been lacking. Here, we have developed a novel automated pipeline to model tumor-stroma interplay, track motility and quantify morphological changes of 3D co-cultures, in real-time live-cell settings. The platform consists of microtissues from prostate cancer cells, combined with CAFs in extracellular matrix that allows biochemical perturbation. Tracking of fibroblast dynamics revealed that CAFs guided the way for tumor cells to invade and increased the growth and invasiveness of tumor organoids. We utilized the platform to determine the efficacy of inhibitors in prostate cancer and the associated tumor microenvironment as a functional unit. Interestingly, certain inhibitors selectively disrupted tumor-CAF interactions, e.g. focal adhesion kinase (FAK) inhibitors specifically blocked tumor growth and invasion concurrently with fibroblast spreading and motility. This complex phenotype was not detected in other standard in vitro models. These results highlight the advantage of our approach, which recapitulates tumor histology and can significantly improve cancer target validation in vitro.

Indexed as

Tumor MicroenvironmentAlgorithmsCell CommunicationCell Culture TechniquesCell LineCell Line, TumorCell MovementCell ProliferationCell TrackingCoculture TechniquesCollagenFibroblastsFocal Adhesion Protein-Tyrosine KinasesGranulocyte-Macrophage Colony-Stimulating FactorHumansMaleCollagenFocal Adhesion Protein-Tyrosine KinasesGranulocyte-Macrophage Colony-Stimulating FactorProtein Kinase Inhibitors3D co-culturecancer associated fibroblast (CAF)focal adhesion kinase (FAK)invasionphenotypic screening

Identifiers

PMID26375443
PMCPMC4745780
OpenAlexW2134427843

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.