Evidence map›Paper›PMID 34573355›Full record

ArticleGenes2021

High Frequency of Tumor Propagating Cells in Fusion-Positive Rhabdomyosarcoma.

Melanie Generali, Sampoorna Satheesha, Peter K Bode, Debora Wanner, Beat W Schäfer, Elisa A Casanova

Open access · goldAbstract read
In one paragraph

Article in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. 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

6 authors at 2 institutions in 1 country.

Melanie GeneraliCenter for Therapy Development and Good Manufacturing Practice, Institute for Regenerative Medicine (IREM), University of Zurich, 8044 Zurich, Switzerland.ORCID 0000-0001-8396-3256
Sampoorna SatheeshaDepartment of Oncology and Children's Research Center, University Children's Hospital Zurich, 8032 Zurich, Switzerland.
Peter K BodeDepartment of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Debora WannerCenter for Therapy Development and Good Manufacturing Practice, Institute for Regenerative Medicine (IREM), University of Zurich, 8044 Zurich, Switzerland.
Beat W SchäferDepartment of Oncology and Children's Research Center, University Children's Hospital Zurich, 8032 Zurich, Switzerland.ORCID 0000-0001-5988-2915
Elisa A CasanovaDivision of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
University of Zurich · CHUniversity Children's Hospital Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Fusion-positive RMS (FPRMS), expressing the PAX3/7-FOXO1, has a worse prognosis compared to the more common fusion-negative RMS (FNRMS). Although several studies reported hierarchical organization for FNRMS with the identification of cancer stem cells, the cellular organization of FPRMS is not yet clear. In this study we investigated the expression of key stem cell markers, developed a sphere assay, and investigated the seven most common FPRMS cell lines for subpopulations of tumor propagating cancer stem-like cells, also called cancer stem cells (CSCs). Moreover, loss- and gain-of-functions of the stem cell genes SOX2, OCT4, and NANOG were investigated in the same cells. Single-cell clonal analysis was performed in vitro as well as in vivo. We found that no stable CSC subpopulation could be enriched in FPRMS. Unlike depletion of PAX3-FOXO1, neither overexpression nor siRNA-mediated downregulation of SOX2, OCT4, and NANOG affected physiology of RMS cells. Every single subclone-derived cell clone initiated tumor growth in mice, despite displaying considerable heterogeneity in gene expression. FPRMS appears to contain a high frequency of tumor propagating stem-like cells, which could explain their higher propensity for metastasis and relapse. Their dependency on PAX3-FOXO1 activity reinforces the importance of the fusion protein as the key therapeutic target.

Indexed as

AnimalsCarcinogenesisCell Line, TumorGain of Function MutationHumansLoss of Function MutationMiceNanog Homeobox ProteinNeoplastic Stem CellsOctamer Transcription Factor-3Oncogene Proteins, FusionPaired Box Transcription FactorsRhabdomyosarcomaSingle-Cell AnalysisSOXB1 Transcription FactorsSpheroids, CellularNanog Homeobox ProteinNANOG protein, humanOctamer Transcription Factor-3Oncogene Proteins, FusionPaired Box Transcription FactorsPAX3-FOXO1A fusion protein, humanPAX7-FOXO1A fusion protein, humanPOU5F1 protein, humanSOX2 protein, humanSOXB1 Transcription Factorscancer stem cellsPAX3-FOXO1Rhabdomyosarcomatumor heterogeneitytumor propagating stem-like cells

Identifiers

PMID34573355
PMCPMC8469567
OpenAlexW3198013693

What OpenQuestion holds

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Registered trials

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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.