Introduction

The U2OS cells line — also known as U-2 OS, U-2OS, U-2-OS, U2-OS, U20-S, U20S, and 2T — is one of the earliest established human cancer cell lines still in active use today. The line was established in the mid-1960s from a moderately differentiated osteosarcoma of the tibia and first described by Pontén and Saksela in 1967 [1]. Its establishment provided researchers with a tractable, adherent, epithelial-morphology model for studying bone neoplasms, tumour biology, and fundamental cell biology. Over subsequent decades, U2OS became a cornerstone of DNA repair research, osteosarcoma drug discovery, cell cycle analysis, and genomic profiling. The cell line retains wild-type TP53 function — a relative rarity among osteosarcoma lines — making it particularly valuable for interrogating p53-dependent pathways, DNA damage responses, and circadian rhythm regulation. With an extensive collection of omics datasets and hundreds of published studies, U2OS remains one of the most cited and characterised human cancer models available to biomedical scientists.

Key Takeaways

• U2OS (Cellosaurus accession CVCL_0042) is a human osteosarcoma cell line established in the mid-1960s from tibial bone tissue and first described in 1967.
• The line carries wild-type TP53, making it a preferred model for p53-dependent cell cycle and DNA damage studies.
• U2OS cells grow as adherent, epithelial-morphology monolayers with a reported doubling time of approximately 25–30 hours (DSMZ ACC-785) to 36 hours (Mohseny et al.).
• The line is extensively profiled across genomics, transcriptomics, proteomics, and drug-screening datasets, including the Cancer Cell Line Encyclopedia.
• U2OS has served as a platform for hundreds of derivative engineered cell lines used in GPCR assays, fluorescent reporter studies, and CRISPR-based functional screens.
• Current research applications span osteosarcoma drug discovery, DNA repair mechanisms, circadian biology, endocytosis, and metabolic reprogramming.

What is U2OS?

U2OS was derived from the tibial bone of a 15-year-old female patient with osteosarcoma. The line was established in the mid-1960s and first reported by Pontén and Saksela in 1967 [1], and was subsequently catalogued among human tumour lines for cancer research [2]. Early immunological characterisation confirmed the absence of HeLa cell contamination [3] and established the cell line's HLA antigen profile [4] [5]. The line grows as an adherent monolayer with epithelial morphology. Reported doubling times differ by source: approximately 25–30 hours according to the DSMZ catalogue entry (ACC-785) and approximately 36 hours in the functional characterisation by Mohseny et al. [13] [61]. It is classified as a moderately differentiated osteosarcoma line that retains wild-type TP53, which distinguishes it from other osteosarcoma lines such as Saos-2, which lacks p53 expression entirely. Comparative characterisation showed that U2OS cells are negative for most classical osteoblastic markers, reflecting their relatively undifferentiated state compared to more mature osteosarcoma lines [6]. The line is microsatellite stable (MSS) and carries a heterozygous PPM1D truncating variant (p.Arg458Ter, c.1372C>T), which is recorded for U2OS in Cellosaurus and DepMap (ACH-000364) [61]. The functional consequence of this class of C-terminally truncating, gain-of-function PPM1D alleles — impairment of the p53-dependent G1 checkpoint — was characterised by Kleiblova et al. [7].

Chromosomal analysis by comparative genomic hybridisation revealed complex genomic aberrations across osteosarcoma lines including U2OS, with an average of 20.8 aberrations per line (range 10–31) [8]. High-resolution array CGH further identified cryptic microaberrations, and U-2 OS showed the fewest such events among the four osteosarcoma lines examined — six, the lowest incidence in the panel — consistent with its wild-type TP53 background, whereas TP53-mutant SAOS-2 carried 17 [9]. The molecular characterisation conducted within the EuroBoNeT consortium confirmed TP53 wild-type status for U2OS and identified homozygous CDKN2A deletion as the single most common event across the bone tumour panel as a whole (15 of 36 lines), strictly associated with absence of p16 protein; no CDKN2A deletion is recorded for U2OS itself in Cellosaurus [10] [61]. Rearrangements of the p53 gene have been documented in primary osteogenic sarcomas and related cell lines [11], and overexpression of wild-type p53 was shown to block cell growth in osteosarcoma cells [12], underscoring the value of the U2OS model for p53 pathway research. Functional studies confirmed that U2OS cells form tumours in vivo after subcutaneous injection, validating their utility as a representative osteosarcoma model [13].

Cell Culture Information

Advantages of U2OS Cells

One of the most significant advantages of U2OS is the retention of wild-type TP53. This property makes the line ideally suited for studying p53-dependent processes, including DNA damage checkpoints, cell cycle arrest, apoptosis, and transcriptional responses to genotoxic stress. Because many osteosarcoma and cancer cell lines carry p53 mutations, U2OS fills a critical niche as a bone tumour model in which p53 pathway pharmacology can be evaluated without the confounding effect of loss-of-function mutations. MDM2 antagonists illustrate why this distinction matters. In a panel of sarcoma cell lines, the MDM2 antagonist Nutlin-3A stabilised p53 and induced downstream p53-dependent transcription and apoptosis efficiently in lines carrying amplified MDM2; in lines with wild-type TP53 but without MDM2 amplification — the configuration found in U2OS — some response to Nutlin was observed, but apoptosis was not induced [14]. A p53-competent bone tumour model therefore allows the contribution of p53 status and of MDM2 dosage to be dissected separately rather than confounded.

U2OS cells are well suited to live-cell microscopy and fluorescent reporter assays owing to their flat, adherent epithelial morphology and relatively large nuclear size. These properties have driven the generation of hundreds of derivative engineered lines — including U2OS-CRISPR-NUP96-SNAP Cells and numerous PathHunter and LanthaScreen variants, all catalogued as child entries of CVCL_0042 [61] — that leverage the parental line's transfectability and optical clarity. The cell line is also a member of multiple major genomic and proteomic profiling initiatives, including the Cancer Dependency Map project (DepMap ACH-000364, which incorporates the Cancer Cell Line Encyclopedia) and the Human Protein Atlas cell atlas panel, providing researchers with rich background datasets against which experimental results can be benchmarked [15] [16] [61].

The line has proven highly amenable to genetic manipulation, supporting stable and transient transfection, CRISPR-Cas9 gene editing, RNAi knockdown, and viral transduction. Its efficient integration of exogenous constructs and robust growth kinetics make it a practical workhorse for high-throughput screening platforms. Cell Painting profiles for 5,259 drugs in U2OS constitute one of the largest morphological reference datasets in chemical biology, and have been combined with thermal proteome profiling to infer compound mechanism of action at scale [17]. This breadth of applicability — spanning bone cancer biology, fundamental cell biology, and drug discovery — underpins the enduring popularity of U2OS.

Limitations of U2OS Cells

Despite its many strengths, U2OS carries chromosomal complexity that can complicate interpretation. Comparative genomic hybridisation across eight osteosarcoma lines revealed an average of 20.8 chromosomal aberrations per line, with U2OS displaying gains and losses across multiple regions [8]. The heterozygous PPM1D gain-of-function truncating variant (p.Arg458Ter) impairs the p53-dependent G1 checkpoint, meaning that while p53 is present and wild-type at the sequence level, its downstream signalling is partially attenuated [7] [61]. Researchers working on precise p53-pathway pharmacology should account for this modifier when interpreting results.

As a moderately differentiated osteosarcoma line, U2OS does not faithfully recapitulate the mature osteoblastic phenotype. Immunocytochemical characterisation showed it is negative for most osteoblastic markers, in contrast to the more mature SaOS-2 Cells line [6]. Studies requiring robust osteogenic differentiation markers or mineralisation responses may therefore find U2OS less representative of late-stage osteoblast biology. Additionally, like all established cell lines, U2OS has accumulated ex vivo adaptations that may not faithfully reflect primary tumour biology, particularly in terms of stroma interactions and three-dimensional architecture [13].

Long-term passaging of U2OS, as with any cell line, carries the risk of genetic drift and phenotypic variation between subclones. Authentication by short tandem repeat profiling is strongly recommended to ensure reproducibility across laboratories [18]. Researchers should also note that U2OS expresses only a subset of classical osteoblastic extracellular matrix proteins, limiting its use as a proxy for bone microenvironment studies that rely on collagen I or other mature osteoblast products.

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Applications

Osteosarcoma Drug Discovery and Therapeutic Screening

U2OS is a primary workhorse for evaluating novel and repurposed compounds against osteosarcoma. Studies have examined the anti-tumour activities of diverse natural and synthetic agents in this line. Curcin C, a type I ribosome-inactivating protein from post-germinated Jatropha curcas seeds, was shown to inhibit U2OS cell proliferation through ROS-mediated apoptosis, autophagy, and arrest in both S and G2/M phase, with the effect attributed to activation of JNK signalling alongside inhibition of the ERK pathway; the ROS scavenger NAC and the JNK inhibitor SP600125 each blunted the response, supporting the proposed cascade [53]. A follow-up study showed that the higher potency of Curcin C relative to Curcin in U2OS is explained largely by LRP1-mediated clathrin-dependent endocytosis, which is available to Curcin C but not to Curcin.

Aloperine, an alkaloid natural product, suppressed proliferation and clonogenicity of both MG-63 and U2OS osteosarcoma cells, induced apoptosis as confirmed by flow cytometry, and inhibited invasion in scratch and transwell assays, with downregulation of MMP-2, MMP-9, PI3K and p-AKT1 [54]. This study highlighted multiple convergent pathways through which natural alkaloids could simultaneously impair growth and metastatic potential. Independently, the natural sweetener metabolite steviol was shown to inhibit U2OS proliferation in a dose- and time-dependent manner, with mechanistic investigation revealing G1-phase cell cycle arrest and a mitochondrial apoptotic pathway indicated by an increased Bax/Bcl-2 ratio [55] — findings that position natural metabolites as candidates for osteosarcoma chemoprevention research.

Tannic acid enhanced the cytotoxic effect of cisplatin in U2OS cells, but the interaction proved strongly ratio-dependent: synergy was observed at tannic acid to cisplatin ratios of 90:10 and 85:15, whereas ratios of 75:25 and 50:50 were antagonistic, and tannic acid alone did not significantly inhibit normal hFOB 1.19 osteoblasts [56]. Any polyphenol-based sensitisation strategy therefore depends on careful dose ratio optimisation rather than simple co-administration. Gallic acid similarly potentiated olaparib-induced cell death and attenuated acquired olaparib resistance in U2OS cells and an olaparib-resistant derivative (U2OS-PIR), inhibiting angiogenesis and modulating cPARP, Bcl-2 and Bax [57], expanding the repertoire of natural compound combinations applicable to osteosarcoma treatment research. Lenvatinib, an approved multi-kinase inhibitor, was shown to induce ferroptosis-related changes in U2OS and 143B cells through a p-STAT3/p53/xCT axis, revealing a novel mechanism by which this agent may suppress osteosarcoma progression beyond its canonical angiogenesis-inhibitory role [19]. Natural killer cell–based immunotherapy was evaluated against a panel of osteosarcoma lines including U2OS, with NKG2D ligand expression correlating with NK-mediated killing efficiency and aerosol interleukin-2 improving organ-specific NK cell activity in vivo [20].

A broader sarcoma drug screen encompassing 63 human lines and over 400 oncology compounds documented U2OS drug sensitivity profiles alongside gene and microRNA expression data, providing a rich pharmacogenomic reference for the field [21]. The landmark Cancer Cell Line Encyclopedia project integrated gene expression, copy number, and sequencing data from nearly 950 lines, including U2OS, and correlated these with drug sensitivity profiles to identify predictive biomarkers of response [15]. A subsequent pharmacogenomic landscape study mapped drug-sensitivity associations onto cancer-driven alterations across more than 1,000 annotated lines, further contextualising U2OS responses within the broader oncology space [22].

The miR-16-1-3p/MDM2/p53 axis has emerged as an important regulator of TGF-β1 signalling output in osteosarcoma. Xue et al. demonstrated that miR-16-1-3p overexpression markedly reduced the proliferative and clonogenic potential of U2OS cells, while its combination with TGF-β treatment strongly enhanced G1-phase arrest and nearly abolished tumour growth capacity [23]. The same study showed that miR-16-1-3p inhibited TGF-β-induced actin remodelling and epithelial-mesenchymal transition-associated changes, and that co-administration increased cisplatin sensitivity in wild-type U2OS cells and reduced tumour nodule volume and metastasis in the chick chorioallantoic membrane model, providing mechanistic insight into how this microRNA suppresses the pro-metastatic arm of TGF-β signalling. Osteoblast-derived extracellular vesicles (OB-EVs) were shown to alter osteosarcoma cell behaviour in a line-dependent manner: in U2OS they reduced metabolic activity (1.30-fold) and proliferation (1.70-fold) while increasing apoptosis (1.15-fold), whereas MG-63 proliferation increased 4.9-fold. The accompanying transcriptomic profiling was performed in MNNG/HOS cells, where 296 genes were differentially expressed, and the authors propose miRNA shuttling as a potentially contributing mechanism that still requires functional validation [24]. Metabolic reprogramming in osteosarcoma was explored through single-cell transcriptomics, identifying Stanniocalcin-2 (STC2) as a core glycolytic regulator validated functionally in MG-63 and U2OS cells using Seahorse extracellular flux analysis [25].

DNA Repair, Cell Cycle Regulation, and DNA Damage Response

U2OS is one of the most widely used models in DNA repair research, largely because its wild-type p53 background allows the full range of p53-dependent damage responses to be interrogated. A genome-scale study mapped the cell cycle-regulated transcriptome of U2OS, identifying 2,140 periodically expressed transcripts corresponding to 1,871 unique genes across multiple synchronous cell cycles [52]. By combining ChIP-seq for the G2/M transcription factor FOXM1 with published ChIP-seq data for E2F1, E2F4, E2F6, GABPA and the DREAM complex, the authors showed that FOXM1 strongly activates promoters of G2/M-phase genes and only weakly activates those induced in S phase, and that a core set of cell cycle genes shared between U2OS and HeLa is bound by multiple cell cycle transcription factors. The dataset established U2OS as a second, independently characterised human model for mapping the cell cycle transcriptome and remains a widely used reference for gene-regulatory studies of the human cell division cycle.

Gain-of-function mutations in PPM1D/Wip1 — the phosphatase that inactivates p53 — produce C-terminally truncated, hyperactive Wip1 and impair the p53-dependent G1 checkpoint after DNA damage; U2OS carries such a truncating allele (p.Arg458Ter) heterozygously [7] [61]. This makes U2OS a useful model for studying how Wip1 truncations confer a selective growth advantage by attenuating the DNA damage response. Individual-cell variability in DNA damage response was quantified in U2OS cells exposed to 2 Gy of photons; by comparing 53BP1 and γH2AX foci in sister nuclei of binucleated cells, Płódowska et al. demonstrated stochastic cell-to-cell noise in repair foci formation superimposed on randomly distributed DNA damage, with noise contributing 28% of total variability for 53BP1 foci and 50% for γH2AX foci [26]. Sister chromatid exchange analysis in soft tissue sarcoma lines, including U2OS comparators, confirmed that endogenous γH2AX formation correlates with genomic instability and may predict responses to DNA-damaging treatments [27].

U2OS cells were employed to investigate somatic CAG repeat expansion in Huntington's disease. Genetic disruption of the MSH3 Y245/K246 IDL-binding pocket significantly reduced DNA interaction and abrogated repeat expansion in a U2OS line expressing mutant HTT exon 1, and pharmacological blockade of the same site reduced repeat expansion in U2OS and, importantly, also slowed expansion in medium spiny neurones derived from HD patient iPSCs [28]. The U2OS DR-GFP derivative line has been widely used for homologous recombination repair assays, and multiple knockout derivatives — including RAD52, TBK1, and OPTN knockouts — have been generated to dissect specific repair pathway components, all catalogued as child entries of CVCL_0042 [61]. The TSC2 tumour suppressor was identified as a stress granule suppressor; in a preprint reporting this work, siRNA-mediated partial reduction of TSC2 in U2OS cells did not induce spontaneous stress granules, in contrast to the complete loss observed in mouse embryonic fibroblasts, establishing TSC2 as a threshold-dependent regulator of stress granule assembly [29]. Genome-wide screens for homozygous deletions and polarity complex gene disruptions in cancer cell line panels have also incorporated U2OS data, contributing to the identification of recessive cancer genes and fragile site signatures [30] [31].

Circadian Biology and Gene Regulation

U2OS has become a leading model for mammalian circadian clock research. The cells exhibit robust, self-sustained circadian rhythms and are routinely used with clock gene luciferase reporters for real-time luminometry. Burke et al. used U2OS cells expressing clock gene luciferase reporters to show that caffeine lengthens the circadian period in a dose-dependent manner, and established through pharmacological dissection and siRNA knockdown that adenosine receptor signalling — rather than ryanodine receptor or phosphodiesterase activity — accounts for the effect [59]. The same system supports chemical screening at scale: a high-throughput screen of existing drugs in U2OS cells found that approximately 5% altered circadian period, identifying dehydroepiandrosterone as a period-shortening compound and implicating ABL1, ABL2 and the BCR kinase in period regulation [60]. These properties have been exploited extensively to characterise the molecular mechanisms governing the core BMAL1/CLOCK transcription-translation feedback loop and its interactions with oncogenic pathways.

A recent preprint investigated the endogenous circadian nature of c-MYC in U2OS cells. By generating a c-MYC reporter and comparing its oscillation phase to BMAL1 and PER2 reporters, Kalyanaraman et al. reported that the c-MYC promoter oscillates rhythmically in U2OS — a line with inherently low MYC levels — and oscillates out of phase relative to the core clock components [32]. A computational model built on these findings suggested that MYC acts as a clock disruptor whose timing minimises its negative impact on circadian timekeeping — a finding with implications for understanding how oncogenic MYC overexpression perturbs circadian physiology. As a preprint, this work has not yet completed peer review. It nonetheless exemplifies the suitability of U2OS for simultaneously probing oncogene function and circadian regulation.

U2OS is telomerase-negative and maintains its telomeres through alternative lengthening of telomeres (ALT), the recombination-based mechanism first documented in a subset of tumours and tumour-derived cell lines by Bryan et al. [58]. This makes it a standard model for ALT research, a mechanism active in a subset of cancers including osteosarcomas. The line is also frequently employed in studies of histone modification dynamics, nuclear architecture, and chromatin organisation, leveraging its large nuclei and optical tractability. Fluorescent-tagged histone and nuclear pore derivatives — including U2OS EGFP-H2B and multiple CRISPR-tagged NUP96 lines derived from U2OS — have enabled quantitative imaging of chromatin and nuclear transport processes with high spatial resolution [61].

Endocytosis and Intracellular Trafficking

U2OS has emerged as a standard model for studying clathrin-mediated endocytosis (CME) and dynamin GTPase activity, owing to its robust receptor internalisation activity and suitability for quantitative fluorescence-based CME assays measuring transferrin-Alexa594 uptake. A series of sulfonadyn compounds — aryl sulfonamides derived from dansylcadaverine analogues — were characterised as GTP-competitive dynamin I and dynamin II inhibitors using U2OS cells as the primary CME assay platform [33]. Michaelis-Menten kinetic analysis in this system confirmed the mechanism of inhibition, and the most potent analogue also exhibited antiepileptic activity in animal models, positioning U2OS-based CME assays as a translational tool for neurological drug discovery.

Separately, the marine-derived hydroxyquinone sesquiterpene bolinaquinone and related naphthoquinone analogues were evaluated for CME inhibitory activity in U2OS cells, with density functional theory-guided structural optimisation yielding analogues with substantially improved potency against both dynamin GTPase and CME [34]. These studies illustrate how U2OS-based CME assays serve as a sensitive and reproducible platform for structure-activity relationship studies on endocytosis inhibitors. The line's consistent receptor expression and predictable internalisation kinetics make it a preferred cell system for this class of research.

The fate of antisense oligonucleotides (ASOs) following cellular uptake was tracked in U2OS cells using live-cell microscopy, ratiometric pH measurements, and three-dimensional focused ion beam scanning electron microscopy. In a preprint reporting this work, Sitarska et al. showed that even under conditions reducing target RNA by over 90%, less than 4% of internalised ASOs reached the nucleus, and that ASOs accumulated in late endosomes, endolysosomes and lysosomes where they induced luminal neutralisation without galectin-3 recruitment or limiting-membrane rupture [35]. The authors propose that productive escape instead occurs earlier in endocytosis, most likely in early or recycling endosomes. U2OS cells were also used in a GLP-1R activation assay — a U2OS line expressing cAMP-sensitive Nomad biosensors — to evaluate the metabolic effects of a phospholipid-formulated bergamot extract, demonstrating the line's utility as an engineered receptor expression platform for natural product pharmacology [36]. Cybrid technology for studying mitochondrial DNA mutations was advanced by validating newly developed mtDNA-free (ρ0) derivatives of HCT116, HT1080 and U2OS as recipient cell lines for transmitochondrial cybrid generation [37].

Proteomics, Genomics, and Multi-Omics Platforms

U2OS has been a key reference cell line in large-scale proteomics initiatives. The first dedicated proteome profile of U2OS was generated by Niforou et al. using two-dimensional gel electrophoresis coupled to MALDI mass spectrometry: approximately 3,000 spots were excised from two 2-DE gels and analysed, yielding the identification of 237 distinct gene products, among them 11 protooncogenes related to the cancerous state of the line [16]. Subsequent mass spectrometry-based work quantified the absolute proteome of this line in interphase and mitosis — described in the publication as a commonly used human cell line and assigned to U2OS in Cellosaurus — showing expression of at least approximately 10,000 proteins spanning seven orders of magnitude in cellular abundance, up to 20 million copies per cell [38] [61]. Comparative proteomics across eleven common cell lines showed that U2OS shares a core of ubiquitously expressed proteins while displaying cell-type-specific variation in functional subsets [39].

Large-scale cell surface proteomics using Cell Surface Capture technology catalogued the surfaceome of U2OS alongside 40 other human cell types (41 human and 31 mouse cell types in total), providing a resource for identifying pharmacologically accessible surface targets [40]. HLA typing and neo-epitope prediction studies incorporated U2OS to support cancer immunotherapy target development [41] [42]. The reverse-phase protein array characterisation of over 650 cancer cell lines included U2OS, demonstrating that phosphoproteomic data provide predictive power for drug sensitivity beyond that available from mRNA measurements alone [43]. The pan-cancer proteomic map covering 949 cell lines further integrated U2OS proteomic data with CRISPR essentiality screens and drug response data, revealing thousands of protein biomarkers of cancer vulnerability [44].

Transcriptome-wide characterisation of 675 cancer cell lines by RNA sequencing catalogued gene fusions, mutation signatures, and non-human sequence expression in U2OS [45]. Next-generation CCLE characterisation expanded profiling to include DNA methylation, histone modification, microRNA expression, and RNA splicing data across 1,072 lines, with U2OS contributing to integrative analyses of molecular features underpinning drug responses [46]. Quantitative proteomics of the CCLE panel identified pathway dysregulation at the protein level that was not apparent from genomic or transcriptomic data alone [47]. Cell Painting combined with Thermal Proteome Profiling in U2OS cells demonstrated a powerful strategy for inferring drug mechanism of action by integrating morphological profiling with unbiased protein target detection [17]. U2OS proteomic datasets are also covered by virome-level quality control: a xeno-proteomics workflow for the untargeted detection of viral proteins in proteomics data was developed as a general screening step, with the authors recommending that every cellular proteome dataset be tested for non-human proteins before publication [48]. Osteosarcoma integrative epigenomic analysis incorporating U2OS identified 350 genes with concordant genetic and epigenetic aberrations, advancing understanding of the regulatory landscape governing bone tumour progression [49]. Protein expression in cell microarrays was also evaluated using U2OS cells embedded in agarose matrices, enabling simultaneous profiling of multiple cell lines in a tissue microarray format [50]. Early marker responses of U2OS cells to extracts of a hyaluronic acid-coated xenogeneic bone graft were characterised by qRT-PCR: RUNX2 was upregulated 2.61-fold (p = 0.01), while no significant effect was reported for COL1A1, and the observed differences in metabolic activity did not remain significant after FDR correction [51]. The authors describe the study as exploratory and call for validation in primary cells and in vivo models.

Conclusion

U2OS (CVCL_0042) is a remarkably versatile human osteosarcoma cell line that has contributed to fundamental advances across bone neoplasms research, DNA repair biology, circadian rhythm science, endocytosis pharmacology, and large-scale omics profiling. Its wild-type TP53 background, adherent epithelial morphology, rapid doubling time, and deep multi-omics characterisation make it an exceptionally well-supported experimental model. From early HLA typing studies to contemporary CRISPR-based functional screens and Cell Painting drug profiling, U2OS has continuously adapted to the needs of the biomedical research community. Researchers seeking a reliable, extensively documented model for osteosarcoma biology, cell cycle regulation, DNA damage response, or high-throughput compound screening will find U2OS an indispensable tool. Explore the full specifications or order U2OS Cells directly at cytion.com.

Key Publications

1. Pontén J, Saksela E (1967) Two established in vitro cell lines from human mesenchymal tumours. International journal of cancer. PMID: 6081590
2. Fogh J (1986) Human tumor lines for cancer research. Cancer investigation. PMID: 3518877
3. Fogh J, Wright WC, Loveless JD (1977) Absence of HeLa cell contamination in 169 cell lines derived from human tumors. Journal of the National Cancer Institute. PMID: 833871
4. Espmark JA, Ahlqvist-Roth L, Särne L (1978) Tissue typing of cells in culture. III. HLA antigens of established human cell lines. Tissue antigens. PMID: 77569
5. Pollack MS, Heagney SD, Livingston PO (1981) HLA-A, B, C and DR alloantigen expression on forty-six cultured human tumor cell lines. Journal of the National Cancer Institute. PMID: 7017212
6. Pautke C, Schieker M, Tischer T (2004) Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts. Anticancer research. PMID: 15736406
7. Kleiblova P, Shaltiel IA, Benada J (2013) Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint. The Journal of cell biology. PMID: 23649806
8. Ozaki T, Neumann T, Wai D (2003) Chromosomal alterations in osteosarcoma cell lines revealed by comparative genomic hybridization and multicolor karyotyping. Cancer genetics and cytogenetics. PMID: 12645653
9. Selvarajah S, Yoshimoto M, Maire G (2007) Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. Cancer genetics and cytogenetics. PMID: 17981215
10. Ottaviano L, Schaefer KL, Gajewski M (2010) Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort. Genes, chromosomes & cancer. PMID: 19787792
11. Masuda H, Miller C, Koeffler HP (1987) Rearrangement of the p53 gene in human osteogenic sarcomas. Proceedings of the National Academy of Sciences of the United States of America. PMID: 2823272
12. Diller L, Kassel J, Nelson CE (1990) p53 functions as a cell cycle control protein in osteosarcomas. Molecular and cellular biology. PMID: 2233717
13. Mohseny AB, Machado I, Cai Y (2011) Functional characterization of osteosarcoma cell lines provides representative models to study the human disease. Laboratory investigation; a journal of technical methods and pathology. PMID: 21519327
14. Müller CR, Paulsen EB, Noordhuis P (2007) Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A. International journal of cancer. PMID: 17354236
15. Barretina J, Caponigro G, Stransky N (2012) The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. PMID: 22460905
16. Niforou KM, Anagnostopoulos AK, Vougas K (2008) The proteome profile of the human osteosarcoma U2OS cell line. Cancer genomics & proteomics. PMID: 18359981
17. Johansson C, Johansson M, Kasi PB (2026) Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action. Molecular systems biology. PMID: 42141265
18. Yu M, Selvaraj SK, Liang-Chu MM (2015) A resource for cell line authentication, annotation and quality control. Nature. PMID: 25877200
19. Yang C, Ma Y, Shen W (2026) Lenvatinib induces ferroptosis-related changes in osteosarcoma cells involving the p-STAT3/p53/xCT axis. Frontiers in oncology. PMID: 42294277
20. Guma SR, Lee DA, Yu L (2014) Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis. Pediatric blood & cancer. PMID: 24136885
21. Teicher BA, Polley E, Kunkel M (2015) Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression. Molecular cancer therapeutics. PMID: 26351324
22. Iorio F, Knijnenburg TA, Vis DJ (2016) A Landscape of Pharmacogenomic Interactions in Cancer. Cell. PMID: 27397505
23. Xue W, Wang Y, Smirnova AV (2026) The miR-16-1-3p suppresses proliferation and invasiveness via the MDM2-p53 axis in TGF-β1 signaling in osteosarcoma. Molecular therapy. Oncology. PMID: 42318056
24. Giacchi L, Ucci A, Zelli V (2026) Effect of Osteoblast-Derived Extracellular Vesicles on Osteosarcoma Cells' Transcriptional Profile: Role of Shuttled miRNAs. Biomedicines. PMID: 42193365
25. Hu X, Wang Q, Lin S (2026) Single-cell transcriptomics reveals glycolytic heterogeneity and identifies STC2 as a key regulator of metabolic reprogramming in osteosarcoma. Molecular and cellular biochemistry. PMID: 42166004
26. Płódowska M, Drzazga D, Węgierek-Ciuk A (2026) Assessing the variation of DNA damage response of individual human cells exposed to photon radiation. Radiation and environmental biophysics. PMID: 42301301
27. Salawu A, Wright K, Al-Kathiri A (2018) Sister Chromatid Exchange and Genomic Instability in Soft Tissue Sarcomas: Potential Implications for Response to DNA-Damaging Treatments. Sarcoma. PMID: 29853780
28. Goold R, Donaldson J, Gidney F (2026) Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion. NAR molecular medicine. PMID: 42317610
29. Ma Y, Farny NG (2026) TSC2 is a stress granule suppressor. bioRxiv. Preprint — not peer reviewed. PMID: 42239325
30. Bignell GR, Greenman CD, Davies H (2010) Signatures of mutation and selection in the cancer genome. Nature. PMID: 20164919
31. Rothenberg SM, Mohapatra G, Rivera MN (2010) A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers. Cancer research. PMID: 20215515
32. Kalyanaraman B, Ganesh D, Kunte VA (2026) c-MYC is Transcribed in a Circadian Manner and Acts a Clock Disruptor whose Timing Minimizes its Impacts. bioRxiv. Preprint — not peer reviewed. PMID: 42244582
33. Jones NC, Robertson MJ, Odell LR (2026) Sulfonadyn Compounds: A Class of Aryl Sulfonamides That Inhibit Dynamin GTPase and Clathrin-Mediated Endocytosis and Are Antiepileptic in Animal Models. ACS chemical biology. PMID: 42313002
34. O'Brien NS, Ghods A, Xue J (2025) From bolinaquinone, a marine hydroxyquinone sesquiterpene, to naphthoquinones with clathrin inhibitory effects. RSC medicinal chemistry. PMID: 41884311
35. Sitarska E, Saminathan A, Scanavachi G (2026) Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage. bioRxiv. Preprint — not peer reviewed. PMID: 42182263
36. Khan A, Mella RM, Villacé P (2026) In Vitro Evaluation of GLP-1R-Associated Activity of a Sustainable Standardized Phospholipid-Formulated Bergamot Extract. Biomedicines. PMID: 42193436
37. Weaver L, Alexeyev MF (2026) An Enhanced Method for Transmitochondrial Cybrid Generation. Cells. PMID: 42193905
38. Beck M, Schmidt A, Malmstroem J (2011) The quantitative proteome of a human cell line. Molecular systems biology. PMID: 22068332
39. Geiger T, Wehner A, Schaab C (2012) Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Molecular & cellular proteomics. PMID: 22278370
40. Bausch-Fluck D, Hofmann A, Bock T (2015) A mass spectrometric-derived cell surface protein atlas. PloS one. PMID: 25894527
41. Boegel S, Löwer M, Bukur T (2014) A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines. Oncoimmunology. PMID: 25960936
42. Scholtalbers J, Boegel S, Bukur T (2015) TCLP: an online cancer cell line catalogue integrating HLA type, predicted neo-epitopes, virus and gene expression. Genome medicine. PMID: 26589293
43. Li J, Zhao W, Akbani R (2017) Characterization of Human Cancer Cell Lines by Reverse-phase Protein Arrays. Cancer cell. PMID: 28196595
44. Gonçalves E, Poulos RC, Cai Z (2022) Pan-cancer proteomic map of 949 human cell lines. Cancer cell. PMID: 35839778
45. Klijn C, Durinck S, Stawiski EW (2015) A comprehensive transcriptional portrait of human cancer cell lines. Nature biotechnology. PMID: 25485619
46. Ghandi M, Huang FW, Jané-Valbuena J (2019) Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. PMID: 31068700
47. Nusinow DP, Szpyt J, Ghandi M (2020) Quantitative Proteomics of the Cancer Cell Line Encyclopedia. Cell. PMID: 31978347
48. Chernobrovkin AL, Zubarev RA (2014) Detection of viral proteins in human cells lines by xeno-proteomics: elimination of the last valid excuse for not testing every cellular proteome dataset for viral proteins. PloS one. PMID: 24618588
49. Kresse SH, Rydbeck H, Skårn M (2012) Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma. PloS one. PMID: 23144859
50. Andersson AC, Strömberg S, Bäckvall H (2006) Analysis of protein expression in cell microarrays: a tool for antibody-based proteomics. The journal of histochemistry and cytochemistry. PMID: 16957166
51. Mayer Y, Abu Sada H, Zigdon Giladi H (2026) Early Osteogenic and Stromal Marker Responses of Osteoblast-like and Bone-Marrow Stromal Cell Lines to a Hyaluronic Acid-Coated Xenogeneic Bone Graft: An Exploratory In Vitro Analysis. Dentistry journal. PMID: 42187668
52. Grant GD, Brooks L 3rd, Zhang X (2013) Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors. Molecular biology of the cell. PMID: 24109597
53. Wang F, Wu P, Qin S (2021) Curcin C inhibit osteosarcoma cell line U2OS proliferation by ROS induced apoptosis, autophagy and cell cycle arrest through activating JNK signal pathway. International journal of biological macromolecules. PMID: 34896468
54. Chen S, Jin Z, Dai L (2017) Aloperine induces apoptosis and inhibits invasion in MG-63 and U2OS human osteosarcoma cells. Biomedicine & pharmacotherapy. PMID: 29080457
55. Chen JM, Zhang J, Xia YM (2018) The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line. Oncology letters. PMID: 29552164
56. Kasiram MZ, Hapidin H, Abdullah H (2022) Tannic acid enhances cisplatin effect on cell proliferation and apoptosis of human osteosarcoma cell line (U2OS). Pharmacological reports. PMID: 34652600
57. Erdogan MK, Usca AB (2025) Gallic Acid Enhances Olaparib-Induced Cell Death and Attenuates Olaparib Resistance in Human Osteosarcoma U2OS Cell Line. Current issues in molecular biology. PMID: 39996825
58. Bryan TM, Englezou A, Dalla-Pozza L (1997) Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nature medicine. PMID: 9359704
59. Burke TM, Markwald RR, McHill AW (2015) Effects of caffeine on the human circadian clock in vivo and in vitro. Science translational medicine. PMID: 26378246
60. Tamai TK, Nakane Y, Ota W (2018) Identification of circadian clock modulators from existing drugs. EMBO molecular medicine. PMID: 29666146
61. Cellosaurus. U2OS (CVCL_0042). SIB Swiss Institute of Bioinformatics. Available at: https://www.cellosaurus.org/CVCL_0042 (accessed 11 August 2026)