Evidence map›Paper›PMID 25646025›Full record

ArticleNeuro-oncology2015

ADAM-9 is a novel mediator of tenascin-C-stimulated invasiveness of brain tumor-initiating cells.

Susobhan Sarkar, Franz J Zemp, Donna Senger, Stephen M Robbins, V Wee Yong

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 62 citations in OpenAlex.

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  13. ADAMDEC1 accelerates GBM progressionFrontiers in oncology · 2022
    Article
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  15. Proteases Regulate Cancer Stem Cell Properties and Remodel Their Microenvironment.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021
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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

5 authors at 1 institution in 1 country.

Susobhan SarkarDepartment of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); The Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (F.J.Z., D.S., S.M.R.).
Franz J ZempDepartment of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); The Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (F.J.Z., D.S., S.M.R.).
Donna SengerDepartment of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); The Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (F.J.Z., D.S., S.M.R.).
Stephen M RobbinsDepartment of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); The Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (F.J.Z., D.S., S.M.R.).
V Wee YongDepartment of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (S.S., V.W.Y.); The Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (F.J.Z., D.S., S.M.R.).
University of Calgary · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundTenascin-C (TNC), an extracellular matrix protein overexpressed in malignant gliomas, stimulates invasion of conventional glioma cell lines (U251, U87). However, there is a dearth of such information on glioma stemlike cells. Here, we have addressed whether and how TNC may regulate the invasiveness of brain tumor-initiating cells (BTICs) that give rise to glioma progenies.

methodsTranswell inserts coated with extracellular matrix proteins were used to determine the role of TNC in BTIC invasion. Microarray analysis, lentiviral constructs, RNA interference-mediated knockdown, and activity assay ascertained the role of proteases in TNC-stimulated BTIC invasion in culture. Involvement of proteases was validated using orthotopic brain xenografts in mice.

resultsTNC stimulated BTIC invasiveness in a metalloproteinase-dependent manner. A global gene expression screen identified the metalloproteinase ADAM-9 as a potential regulator of TNC-stimulated BTIC invasiveness, and this was corroborated by an increase of ADAM-9 protein in 4 glioma patient-derived BTIC lines. Notably, RNA interference to ADAM-9, as well as inhibition of mitogen-activated protein kinase 8 (c-Jun NH2-terminal kinase), attenuated TNC-stimulated ADAM-9 expression, proteolytic activity, and BTIC invasiveness. The relevance of ADAM-9 to tumor invasiveness was validated using resected human glioblastoma specimens and orthotopic xenografts where elevation of ADAM-9 and TNC expression was prominent at the invasive front of the tumor.

conclusionsThis study has identified TNC as a promoter of the invasiveness of BTICs through a mechanism involving ADAM-9 proteolysis via the c-Jun NH2-terminal kinase pathway.

Indexed as

ADAM ProteinsAnimalsBrain NeoplasmsCell Line, TumorGlioblastomaHumansMAP Kinase Signaling SystemMembrane ProteinsMiceNeoplasm InvasivenessNeoplastic Stem CellsTenascinADAM9 protein, humanADAM ProteinsMembrane ProteinsTenascinextracellular matrixgliomametalloproteinasesproteolysisstem cell

Identifiers

PMID25646025
PMCPMC4490870
OpenAlexW2138178015

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.