Evidence map›Paper›PMID 34686335›Full record

ArticleCell reports2021

Marker-free lineage tracing reveals an environment-instructed clonogenic hierarchy in pancreatic cancer.

Sophie C Lodestijn, Daniël M Miedema, Kristiaan J Lenos, Lisanne E Nijman, Saskia C Belt, Khalid El Makrini, Maria C Lecca, Cynthia Waasdorp, Tom van den Bosch, Maarten F Bijlsma and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Sophie C LodestijnAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Daniël M MiedemaAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Kristiaan J LenosAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Lisanne E NijmanAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Saskia C BeltAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Khalid El MakriniAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Maria C LeccaAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Cynthia WaasdorpAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Tom van den BoschAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Maarten F BijlsmaAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands. Electronic address: m.f.bijlsma@amsterdamumc.nl.
Louis VermeulenAmsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands. Electronic address: l.vermeulen@amsterdamumc.nl.

Funding

Worldwide Cancer Research 14-1164
6 · The paper itself

Abstract

Effective treatments for pancreatic ductal adenocarcinoma (PDAC) are lacking, and targeted agents have demonstrated limited efficacy. It has been speculated that a rare population of cancer stem cells (CSCs) drives growth, therapy resistance, and rapid metastatic progression in PDAC. These CSCs demonstrate high clonogenicity in vitro and tumorigenic potential in vivo. However, their relevance in established PDAC tissue has not been determined. Here, we use marker-independent stochastic clonal labeling, combined with quantitative modeling of tumor expansion, to uncover PDAC tissue growth dynamics. We find that in contrast to the CSC model, all PDAC cells display clonogenic potential in situ. Furthermore, the proximity to activated cancer-associated fibroblasts determines tumor cell clonogenicity. This means that the microenvironment is dominant in defining the clonogenic activity of PDAC cells. Indeed, manipulating the stroma by Hedgehog pathway inhibition alters the tumor growth mode, revealing that tumor-stroma crosstalk shapes tumor growth dynamics and clonal architecture.

Indexed as

Cell LineageTumor MicroenvironmentAnilidesAnimalsAntineoplastic AgentsCancer-Associated FibroblastsCarcinoma, Pancreatic DuctalCell CommunicationCell Line, TumorCell ProliferationFemaleHedgehog ProteinsHumansMaleMiceMice, Inbred NODAnilidesAntineoplastic AgentsHedgehog ProteinsHhAntag691Pyridinescancer stem cellslineage tracingpancreatic cancerPDACstem cell dynamicsstroma

Identifiers

PMID34686335

What OpenQuestion holds

Textmetadata
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.