Evidence map›Paper›PMID 34830078›Full record

ArticleInternational journal of molecular sciences2021

Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells.

Reza Haschemi, Dennis Kobelt, Elisabeth Steinwarz, Martin Schlesinger, Ulrike Stein, Gerd Bendas

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

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

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  11. Prognostic circulating proteomic biomarkers in colorectal liver metastases.Computational and structural biotechnology journal · 2023
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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

6 authors at 2 institutions in 1 country.

Reza HaschemiPharmaceutical Department, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Dennis KobeltExperimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.ORCID 0000-0002-9373-0648
Elisabeth SteinwarzPharmaceutical Department, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Martin SchlesingerPharmaceutical Department, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Ulrike SteinExperimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.ORCID 0000-0001-7006-282X
Gerd BendasPharmaceutical Department, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.ORCID 0000-0002-8667-7201
University of Bonn · DEGerman Cancer Research Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted prognostic biomarker. However, the impact of MACC1 on platelet activation has not yet been addressed. Here, we investigated the activation of platelets by human CRC cells upon MACC1 modulation, indicated by platelet aggregation and granule release. These approaches led to the identification of insulin-like growth factor binding protein-2 (IGFBP2) as a functional downstream molecule of MACC1, affecting communication with platelets. This was confirmed by an shRNA-mediated IGFBP2 knockdown, while maintaining MACC1 activity. Although IGFBP2 displayed an attenuated platelet activation potential, obviously by scavenging IGF-I as a platelet costimulatory mediator, the MACC1/IGFBP2 axis did not affect the thrombin formation potential of the cells. Furthermore, the IGFBP2/MACC1-driven cell migration and invasiveness was further accelerated by platelets. The key role of IGFBP2 for the metastatic spread in vivo was confirmed in a xenograft mouse model. Data provide evidence for IGFBP2 as a downstream functional component of MACC1-driven metastasis, linking these two accepted oncogenic biomarkers for the first time in a platelet context.

Indexed as

Cell CommunicationAnimalsBlood PlateletsCell Line, TumorColorectal NeoplasmsFemaleHumansInsulin-Like Growth Factor Binding Protein 2MiceMice, Inbred NODMice, SCIDNeoplasm MetastasisNeoplasm ProteinsTrans-ActivatorsIGFBP2 protein, humanInsulin-Like Growth Factor Binding Protein 2MACC1 protein, humanNeoplasm ProteinsTrans-Activatorscolorectal cancerIGFBP2MACC1metastasisplatelets

Identifiers

PMID34830078
PMCPMC8624049
OpenAlexW3214197925

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.