Evidence map›Paper›PMID 30509303›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

HDAC2 depletion promotes osteosarcoma's stemness both in vitro and in vivo: a study on a putative new target for CSCs directed therapy.

Marcella La Noce, Francesca Paino, Luigi Mele, Gianpaolo Papaccio, Tarik Regad, Angela Lombardi, Federica Papaccio, Vincenzo Desiderio, Virginia Tirino

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.3field-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

37 citing papers in PubMed, 71 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 3 institutions in 2 countries.

Marcella La NoceDipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Università degli Studi della Campania "L. Vanvitelli", Napoli, via L. Armanni, 5, 80138, Naples, Italy.
Francesca PainoDipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Via Commenda,10, 20122, Milan, Milano, Italy.
Luigi MeleDipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Università degli Studi della Campania "L. Vanvitelli", Napoli, via L. Armanni, 5, 80138, Naples, Italy.
Gianpaolo PapaccioDipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Università degli Studi della Campania "L. Vanvitelli", Napoli, via L. Armanni, 5, 80138, Naples, Italy. gianpaolo.papaccio@unicampania.it.
Tarik RegadThe John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
Angela LombardiDipartimento di Medicina di Precisione, Università degli Studi della Campania "L. Vanvitelli", Napoli, Via L. De Crecchio, 7, 80138, Naples, Italy.
Federica PapaccioDipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale "F. Magrassi", Università degli Studi della Campania "L. Vanvitelli", via S. Pansini-Cappella Cangiani, 80131, Naples, Italy.
Vincenzo DesiderioDipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Università degli Studi della Campania "L. Vanvitelli", Napoli, via L. Armanni, 5, 80138, Naples, Italy.
Virginia TirinoDipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Università degli Studi della Campania "L. Vanvitelli", Napoli, via L. Armanni, 5, 80138, Naples, Italy. virginia.tirino@unicampania.it.
University of Campania "Luigi Vanvitelli" · ITNottingham Trent University · GBUniversity of Milan · IT

Funding

MIUR-EU PON 01_02834MIUR-EU PRIN 20102M7T8X_002
6 · The paper itself

Abstract

backgroundCancer stem cells (CSCs) play a key role in cancer initiation, progression and chemoresistance. Epigenetic alterations have been identified as prominent factors that contribute to the CSCs phenotype. Here, we investigated the effects of the HDAC inhibitor valproic acid (VPA) and the demethylating agent, 5'azacytidine (DAC) on the stem phenotype of MG63 and Saos2 osteosarcoma cell lines.

methodsSaos2 and MG63 cells were treated with DAC and VPA, alone and in combination. Untreated and treated cells were examined for stemness phenotype by cytometry and real-time PCR. Sarcospheres and colonies formation were also evaluated. Moreover, histone modification and methylation were tested by flow cytomery and western blotting. HDAC2 depleted cells were examined for stemness phenotype and their ability to generate tumors in NOD/SCID IL2R-gamma-0 (NSG) mice. HDAC2 expression on human osteosarcoma tissues was evaluated.

resultsWe found that DAC and VPA induce an increased expression of stem markers including CD133, OCT4, SOX2 and NANOG, and an increased ability in sarcospheres and colonies formation efficiency. Interestingly, we showed that DAC and VPA treatment decreased repressive histone markers, while increased the active ones. These histone modifications were also associated with an increase of acetylation of histones H3, a decrease of DNA global methylation, HDAC2 and DNMT3a. Furthermore, HDAC2 silenced-MG63 and Saos2 cells acquired a stem phenotype, and promoted in vivo tumorigenesis. In human osteosarcoma tissues, HDAC2 was strongly expressed in nucleus.

conclusionsCollectively, our results suggest that VPA and DAC induce an expansion of osteosarcoma CSCs, and we report for the first time that HDAC2 is a key factor regulating both CSCs phenotype and in vivo cancer growth. In conclusion, we have identified HDAC2 as a potential therapeutic target in human osteosarcoma treatment.

Indexed as

AnimalsAzacitidineBone NeoplasmsCell Line, TumorDNA MethylationHeterograftsHistone Deacetylase 2HumansMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsOsteosarcomaTransfectionValproic AcidAzacitidineHDAC2 protein, humanHistone Deacetylase 2Valproic AcidCancer stem cellsDNMT3aHDAC2MethylationOsteosarcomas

Identifiers

PMID30509303
PMCPMC6276256
OpenAlexW2902669105

What OpenQuestion holds

Textmetadata
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.