Evidence map›Paper›PMID 22183788›Full record

ArticleJournal of neuroscience research2012

Calpain 2 is required for the invasion of glioblastoma cells in the zebrafish brain microenvironment.

Sangeet Lal, Jane La Du, Robert L Tanguay, Jeffrey A Greenwood

Abstract read
In one paragraph

Article in Journal of neuroscience research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
–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

43 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  17. Benefits of Zebrafish Xenograft Models in Cancer Research.Frontiers in cell and developmental biology · 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

4 authors.

Sangeet LalDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Jane La Du
Robert L Tanguay
Jeffrey A Greenwood

Funding

Reducing Susceptibility to Environmental Stress Throughout the Life SpanP30ES000210 · NIEHS · OREGON STATE UNIVERSITY · PI BECKMAN, JOSEPH S · 1985 to 2015
$21.4M
Phosphoinositide Regulation of Focal Adhesion StructureR01GM063711 · NIGMS · OREGON STATE UNIVERSITY · PI GREENWOOD, JEFFREY A · 2002 to 2006
$1.1M
NIEHS NIH HHS P30 ES000210NIEHS NIH HHS P30 ES00210NIGMS NIH HHS R01 GM063711
6 · The paper itself

Abstract

Glioblastoma is an aggressive primary brain tumor with a 5-year survival rate of less than 5%. The ability of glioblastoma cells to invade surrounding brain tissue presents the primary challenge for the success of focal therapeutic approaches. We previously reported that the calcium-activated protease calpain 2 is critical for glioblastoma cell invasion in vitro. Here, we show that expression of calpain 2 is required for the dispersal of glioblastoma cells in a living brain microenvironment. Knockdown of calpain 2 resulted in a 2.9-fold decrease in the invasion of human glioblastoma cells in zebrafish brain. Control cells diffusely migrated up to 450 μm from the site of injection, whereas knockdown cells remained confined in clusters. The invasion study was repeated in organotypic mouse brain tissues, and calpain 2 knockdown cells demonstrated a 2.3-fold lower area of dispersal compared with control cells. In zebrafish brain, glioblastoma cells appeared to migrate in part along the blood vessels of the host. Furthermore, angiogenesis was detected in 27% of zebrafish injected with control cells, whereas only 12.5% of fish receiving knockdown cells showed the formation of new vessels, suggesting a role for calpain 2 in tumor cell angiogenesis. Consistent with the progression of glioblastoma in humans, transplanted tumor cells were not observed to metastasize outside the brain of zebrafish. This study demonstrates that calpain 2 expression is required for the dispersal of glioblastoma cells within the dynamic microenvironment of the brain, identifying zebrafish as a valuable orthotopic system for studying glioblastoma cell invasion.

Indexed as

AnimalsAnimals, Genetically ModifiedBrain NeoplasmsCalpainCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaGreen Fluorescent ProteinsHumansIn Vitro TechniquesNeoplasm TransplantationNeovascularization, PathologicOligonucleotide Array Sequence AnalysisProto-Oncogene Protein c-fli-1CalpainCAPN2 protein, humanFLI1 protein, humanGreen Fluorescent ProteinsProto-Oncogene Protein c-fli-1RNA, Small Interfering

Identifiers

PMID22183788
PMCPMC3274595

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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.