Evidence map›Paper›PMID 23446043›Full record

ArticleBMC cancer2013

3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing.

Paola Longati, Xiaohui Jia, Johannes Eimer, Annika Wagman, Michael-Robin Witt, Stefan Rehnmark, Caroline Verbeke, Rune Toftgård, Matthias Löhr, Rainer L Heuchel

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.

0numbers the graph read from it
0cells of the map it votes in
210citing papers in PubMed
15.2field-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

210 citing papers in PubMed, 380 citations in OpenAlex.

  1. Article
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  7. Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Article
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  11. Beyond monolayers: a comparative analysis of 2D cell cultures and 3DFrontiers in bioengineering and biotechnology · 2026
    Review
  12. Pirfenidone Attenuates Fibrosis and Neovascularization in 3D Spheroid-Laden Hydrogel Culture.Journal of tissue engineering and regenerative medicine · 2026
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Reversible chemoresistance of pancreatic cancer grown as spheroids.Journal of chemotherapy (Florence, Italy) · 2025
    Article
  19. Article
  20. Review

150 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

10 authors at 2 institutions in 1 country.

Paola LongatiCLINTEC, Karolinska Institutet, Stockholm 14186, Sweden.
Xiaohui Jia
Johannes Eimer
Annika Wagman
Michael-Robin Witt
Stefan Rehnmark
Caroline Verbeke
Rune Toftgård
Matthias Löhr
Rainer L Heuchel
Karolinska Institutet · SEAxcentua (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance.

methodsSeveral established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine.

resultsComparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect.

conclusionsWe developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.

Indexed as

PhenotypeAnimalsAntineoplastic AgentsCarcinoma, Pancreatic DuctalCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmDrug Screening Assays, AntitumorEnergy MetabolismExtracellular Matrix ProteinsHumansLactic AcidMicePancreatic NeoplasmsSpheroids, CellularTumor Cells, CulturedAntineoplastic AgentsExtracellular Matrix ProteinsLactic Acid

Identifiers

PMID23446043
PMCPMC3617005
OpenAlexW2057280155

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.