Evidence map›Paper›PMID 27542270›Full record

ArticleOncotarget2016

Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer.

Larissa E Hillebrand, Fee Bengsch, Jochen Hochrein, Jan Hülsdünker, Julia Bender, Marie Follo, Hauke Busch, Melanie Boerries, Thomas Reinheckel

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Proteases Regulate Cancer Stem Cell Properties and Remodel Their Microenvironment.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021
    Review
  3. Review
  4. 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

9 authors at 3 institutions in 1 country.

Larissa E HillebrandInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Fee BengschInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Jochen HochreinInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Jan HülsdünkerInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Julia BenderInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Marie FolloDepartment of Hematology/Oncology, Core Facility, University Medical Center, Freiburg, Germany.
Hauke BuschInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Melanie BoerriesInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Thomas ReinheckelInstitute of Molecular Medicine and Cell Research, Medical Faculty, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
University Medical Center Freiburg · DEUniversity of Freiburg · DEUniversity Hospital Heidelberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45-, showed a high tumorigenicity compared to non-CD24+CD90+CD45- cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45- TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45- cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45- cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas.

Indexed as

ProteolysisAnimalsCarcinogenesisCD24 AntigenCell Culture TechniquesCell ProliferationCell SeparationCell Transformation, NeoplasticFemaleFlow CytometryGene Expression RegulationLeukocyte Common AntigensMammary Neoplasms, AnimalMatrix Metalloproteinase 14MiceMice, TransgenicCD24 AntigenCd24a protein, mouseLeukocyte Common AntigensMatrix Metalloproteinase 14Mmp14 protein, mousePeptide HydrolasesPtprc protein, mouseThy-1 Antigensbreast cancerdegradomematrix metalloproteinaseproteolysis

Identifiers

PMID27542270
PMCPMC5295428
OpenAlexW2508883697

What OpenQuestion holds

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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.