Evidence map›Paper›PMID 26701791›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2016

Human IGF1 pro-forms induce breast cancer cell proliferation via the IGF1 receptor.

Mauro De Santi, Giosuè Annibalini, Elena Barbieri, Anna Villarini, Luciana Vallorani, Serena Contarelli, Franco Berrino, Vilberto Stocchi, Giorgio Brandi

Open access · greenAbstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Mauro De SantiDepartment of Biomolecular Sciences, Hygiene Unit, University of Urbino Carlo Bo, Via S. Chiara, 27 - 61029, Urbino, PU, Italy. mauro.desanti@uniurb.it.
Giosuè AnnibaliniDepartment of Biomolecular Sciences, Exercise and Health Sciences Unit, University of Urbino Carlo Bo, Urbino, PU, Italy.
Elena BarbieriDepartment of Biomolecular Sciences, Exercise and Health Sciences Unit, University of Urbino Carlo Bo, Urbino, PU, Italy.
Anna VillariniEpidemiology & Prevention Unit, Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Luciana ValloraniDepartment of Biomolecular Sciences, Exercise and Health Sciences Unit, University of Urbino Carlo Bo, Urbino, PU, Italy.
Serena ContarelliDepartment of Biomolecular Sciences, Exercise and Health Sciences Unit, University of Urbino Carlo Bo, Urbino, PU, Italy.
Franco BerrinoEpidemiology & Prevention Unit, Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Vilberto StocchiDepartment of Biomolecular Sciences, Exercise and Health Sciences Unit, University of Urbino Carlo Bo, Urbino, PU, Italy.
Giorgio BrandiDepartment of Biomolecular Sciences, Hygiene Unit, University of Urbino Carlo Bo, Via S. Chiara, 27 - 61029, Urbino, PU, Italy.
University of Urbino · ITFondazione IRCCS Istituto Nazionale dei Tumori · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIGF1 is a key regulator of tissue growth and development and has been implicated in the initiation and progression of various cancers, including breast cancer. Through IGF1 mRNA splicing different precursor pro-peptides, i.e., the IGF1Ea, IGF1Eb and IGF1Ec pro-forms, are formed whose biological roles in the pathogenesis of breast cancer have not been established yet. The objective of this study was to assess the biological activity of the IGF1 pro-forms in human breast cancer-derived cells.

methodsThe different IGF1 pro-forms were generated through transient transfection of HEK293 cells with the respective vector constructs. The resulting conditioned media were applied in vitro to MCF7, T47D and ZR751 breast cancer-derived cell cultures. The recombinant human IGF1 pro-forms were also tested for their binding affinity to an anti-IGF1 specific antibody by immunoprecipitation. To determine whether the IGF1 pro-forms induce cell proliferation, mature IGF1 was neutralised in HEK293-derived conditioned media.

resultsWe found that the IGF1 pro-forms were the only forms that were produced intra-cellularly, whereas both mature IGF1 and the IGF1 pro-forms were detected extra-cellularly. We also found that E peptides can impair the IGF1 pro-form binding affinity for the anti-IGF1 antibody and, thus, hamper an accurate measurement of the IGF1 pro-forms. Additionally, we found that the IGF1 antibody can completely inhibit IGF1-induced breast cancer cell proliferation and IGF1 receptor (IGF1R) phosphorylation, wheras the same antibody was found to only partially inhibit the biological activity of the pro-forms. Moreover, we found that the IGF1 pro-form activities can completely be inhibited by neutralising the IGF1R. Finally, we compared the bioactivity of the IGF1 pro-forms to that of mature IGF1, and found that the IGF1 pro-forms were less capable of phosphorylating the IGF1R in the breast cancer-derived cells tested.

conclusionsOur data indicate that IGF1 pro-forms can induce breast cancer cell proliferation via the IGF1R, independent from the mature IGF1 form. These results underline the importance of an accurate assessment of the presence of IGF1 pro-forms within the breast cancer microenvironment.

Indexed as

Breast NeoplasmsCell Line, TumorCell ProliferationCulture MediaExtracellular Signal-Regulated MAP KinasesFemaleHEK293 CellsHumansInsulin-Like Growth Factor IModels, BiologicalPeptidesPhosphorylationProtein PrecursorsProto-Oncogene Proteins c-aktReceptor, IGF Type 1TransfectionCulture MediaExtracellular Signal-Regulated MAP KinasesInsulin-Like Growth Factor IPeptidespro-insulin-like growth factor IProtein PrecursorsProto-Oncogene Proteins c-aktReceptor, IGF Type 1Breast cancerIGF1 pro-formsIGF1 receptor

Identifiers

PMID26701791
PMCPMC13001881
OpenAlexW2302659455

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.