ArticlePloS one2016
Analysis of Gene Expression in 3D Spheroids Highlights a Survival Role for ASS1 in Mesothelioma.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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.
Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Keratocyte Gene Expression Shaped by ECM Dimensionality: Evidence for Enhanced Quiescence in 3D Culture.Bioengineering (Basel, Switzerland) · 2026Article
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Immunotherapy resistance and strategies in malignant pleural mesothelioma.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Review
- Genes and proteins expression profile of 2D vs 3D cancer models: a comparative analysis for better tumor insights.Cytotechnology · 2025Review
- Article
- 3D cell subculturing pillar dish for pharmacogenetic analysis and high-throughput screening.Materials today. Bio · 2023Article
- BAP1 Loss Is Associated with Higher ASS1 Expression in Epithelioid Mesothelioma: Implications for Therapeutic Stratification.Molecular cancer research : MCR · 2023Article
- Article
- EGFR-targeted bacteriophage lambda penetrates model stromal and colorectal carcinoma tissues, is taken up into carcinoma cells, and interferes with 3-dimensional tumor formation.Frontiers in immunology · 2022Article
- Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids.Oncotarget · 2021Article
- Review
- Single cell organization and cell cycle characterization of DNA stained multicellular tumor spheroids.Scientific reports · 2021Article
- Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.Frontiers in oncology · 2021Review
- Article
- The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models.Frontiers in oncology · 2020Review
- Apoptosis Induction and Alteration of Cell Adherence in Human Lung Cancer Cells under Simulated Microgravity.International journal of molecular sciences · 2019Article
- Short-term 3D culture systems of various complexity for treatment optimization of colorectal carcinoma.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. A total of 209 genes were differentially expressed in common by the three cell lines in 3D (138 upregulated and 71 downregulated), although a clear resistance pathway was not apparent. We then compared the list of 3D genes with two publicly available datasets of gene expression of 56 pleural mesotheliomas compared to normal tissues. Interestingly, only three genes were increased in both 3D spheroids and human tumors: argininosuccinate synthase 1 (ASS1), annexin A4 (ANXA4) and major vault protein (MVP); of these, ASS1 was the only consistently upregulated of the three genes by qRT-PCR. To measure ASS1 protein expression, we stained 2 sets of tissue microarrays (TMA): one with 88 pleural mesothelioma samples and the other with additional 88 pleural mesotheliomas paired with matched normal tissues. Of the 176 tumors represented on the two TMAs, ASS1 was expressed in 87 (50%; staining greater than 1 up to 3+). For the paired samples, ASS1 expression in mesothelioma was significantly greater than in the normal tissues. Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.