Evidence map›Paper›PMID 33083904›Full record

ArticleJournal of cancer research and clinical oncology2021

Conditional knockdown of integrin beta-3 reveals its involvement in osteolytic and soft tissue lesions of breast cancer skeletal metastasis.

Marineta Kovacheva, Michael Zepp, Stefan Berger, Martin R Berger

Open access · hybridAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 40 citations in OpenAlex.

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  12. Loss ofInternational journal of molecular sciences · 2023
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  16. EccDNA-orientedAnnals of translational medicine · 2022
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  17. Muscle and Bone Defects in Metastatic Disease.Current osteoporosis reports · 2022
    Review
  18. Article
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  20. Identification ofFrontiers in immunology · 2022
    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

4 authors at 2 institutions in 1 country.

Marineta KovachevaToxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Michael ZeppToxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Stefan BergerDepartment of Molecular Biology, Central Institute of Mental Health, 68159, Mannheim, Germany.
Martin R BergerToxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. m.berger@dkfz.de.ORCID http://orcid.org/0000-0002-3783-5365
German Cancer Research Center · DECentral Institute of Mental Health · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Integrin β3 (ITGB3) is probably related to skeletal metastasis, which is the most frequent complication in breast cancer progression. We aimed to define its role and suitability as target for anti-metastatic therapy. We generated two MDA-MB-231 cell clones with conditional miRNA-mediated ITGB3 knockdown for analyzing the resulting effects in vitro regarding mRNA expression, proliferation and migration, as well the impact on skeletal metastasis in a nude rat model. Furthermore, ITGB3 levels were analyzed in exosomes from plasma of rats with skeletal metastases, and from MDA-MB-231 cells incubated with these vesicles, as well as from exosomes secreted by cells with conditional ITGB3 knockdown. This inhibition of ITGB3 expression decreased cellular proliferation and more distinctly inhibited cellular migration. Reduction and even complete remissions of respective soft tissue and osteolytic lesions were detected after ITGB3 knockdown in vivo. Furthermore, ITGB3 levels were increased in exosomes isolated from plasma of rats harboring MDA-MB-231 lesions as well as in respective cells incubated with these vesicles in vitro. ITGB3 was distinctly decreased in exosomes from cells with ITGB3 knockdown. The observed in vitro and in vivo anti-ITGB3 effects can be explained by downregulation of specific genes, which have roles in angiogenesis (NPTN, RRM2), tumor growth (NPTN), energy metabolism (ISCA1), cytokinesis (SEPT11), migration (RRM2, STX6), cell proliferation, invasiveness, senescence, tumorigenesis (RRM2) and vesicle trafficking (SEPT11, STX6). ITGB3 has a role in breast cancer skeletal metastasis via gene expression modulation, as mirrored for ITGB3 in exosomes, thus it could serve as target for anti-metastatic therapy.

Indexed as

Bone NeoplasmsBreast NeoplasmsIntegrin beta3OsteolysisAnimalsCell Line, TumorExosomesFemaleHumansMaleMammary Neoplasms, ExperimentalRatsSoft Tissue InjuriesIntegrin beta3ITGB3 protein, humanBreast cancerConditional ITGB3 knockdownDoxycyclineIntegrinsSkeletal metastasis

Identifiers

PMID33083904
PMCPMC7817553
OpenAlexW3093711849

What OpenQuestion holds

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LicenceCC BY
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.