Evidence map›Paper›PMID 41039593›Full record

ArticleCell communication and signaling : CCS2025

Establishment of a mouse hepatocellular carcinoma tumoroid panel recapitulating inter- and intra- heterogeneity for disease modelling and combinatorial drug discovery.

Margherita Grattarola, Nicolas Pons, Floriane Cannet, Müge Kaya, Abdessamad El Kaoutari, Christian Morel, Aurélie Dobric, Jean-Paul Borg, Celia Sequera, Flavio Maina

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. 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

10 authors.

Margherita Grattarola *Aix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.ORCID http://orcid.org/0000-0003-4172-7866
Nicolas Pons *Aix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.ORCID http://orcid.org/0000-0003-1691-3915
Floriane CannetAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
Müge KayaAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
Abdessamad El KaoutariAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.ORCID http://orcid.org/0000-0003-2334-3121
Christian MorelAix Marseille Univ, CNRS/IN2P3, CPPM, Marseille, France.ORCID http://orcid.org/0000-0001-5359-6504
Aurélie DobricAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
Jean-Paul BorgAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.ORCID http://orcid.org/0000-0001-8418-3382
Celia SequeraAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.ORCID http://orcid.org/0000-0001-6409-3910
Flavio MainaAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France. flavio.maina@univ-amu.fr.ORCID http://orcid.org/0000-0001-6100-4695

Funding

Association pour la Recherche sur le Cancer ARCPGA2023010005822_6352INCa 2020-11/279/NI-KAITMO Cancer 21CD125-00
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is characterised by a remarkable molecular heterogeneity and resistance to current therapies. The use of established HCC cell lines has been the gold standard for fundamental and drug screening studies. However, each cell line is a single clone lacking cell heterogeneity, thus limiting the evaluation of anticancer efficacy, with a consequent drop of translatability regarding their clinical effectiveness, notably in relation to HCC complexity. Additionally, 2D monolayer cultures do not reproduce cell-cell and cell-matrix interactions, known to influence biological, molecular, and signalling features of cancer cells and their response to treatments.

methodsA panel of primary HCC cells and tumoroids was generated from primary tumours of the Alb-R26Met mice. Morphological, molecular, and signalling features were evaluated by histology, imaging, RT-qPCR, and western blots. Proliferation capability and drug efficiency were evaluated through cell viability assays.

resultsWe report the establishment of eight primary cells from distinct spontaneous HCC of the Alb-R26Met mouse model. By evaluating their morphological, molecular, and signalling pathway characteristics, we illustrate their inter-/intra- tumour heterogeneity. We show their biological features by reporting their distinct proliferation rate and resistance to RTK inhibitors used in the clinic for HCC treatments. Moreover, we document their ability to generate tumoroids, optimizing a protocol for HCC 3D cultures. The robustness of the methodology we established is illustrated by the maintenance of morphological, molecular, and growth features along several passages. Finally, we exemplify the value of this tumoroid panel for anticancer treatment evaluation by assessing the effectiveness of a new combinatorial therapy for HCC that we recently identified.

conclusionsOutcomes provide a robust methodology for the generation of HCC tumoroids and designate such heterogeneous tumoroid panel as a valuable setting for disease modelling and drug discovery.

Indexed as

Carcinoma, HepatocellularDrug DiscoveryLiver NeoplasmsOrganoidsAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalDisease Models, AnimalHumansMiceSignal TransductionAntineoplastic Agents3D drug testingCancer heterogeneityCancer mouse modelDisease modellingDrug discoveryHepatocellular carcinomaLiver cancerOrganoidPrimary HCC cellsResistanceTumoroid

Identifiers

PMID41039593
PMCPMC12492699

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LicenceCC BY-NC-ND
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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.