ArticlePloS one2014
Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01536054 (A Phase I Clinical Trial of mTOR Inhibition With Sirolimus for Enhancing ALVAC), which is not on this map. Cited by 230 papers, 2 of them syntheses that pooled it.
What it found
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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.
A Phase I Clinical Trial of mTOR Inhibition With Sirolimus for Enhancing ALVAC(2)-NY-ESO-1(M)/TRICOM Vaccine Induced Anti-Tumor Immunity in Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Who cites it
230 citing papers in PubMed, 2 syntheses or guidelines pooled it, 363 citations in OpenAlex.
- Modeling metastasis and predicting drug response with malignant effusion-derived organoids: a systematic review and quantitative assessment.Journal of translational medicine · 2026Pooled it
- PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Pooled it
- Evaluating carboplatin and PARP inhibitor combination efficacy using high-grade serous carcinoma spheroids and organoids.Cancer biology & therapy · 2026Article
- Benchmarking Ultra-Low Attachment and Photopatterned GelMA 3D Culture Platforms for Modeling Cancer Stemness in High-Grade Serous Ovarian Cancer.Biotechnology journal · 2026Article
- Tumor-suppressive circRNAs in colorectal cancer spheroids and patients.Journal of the Chinese Medical Association : JCMA · 2026Article
- POU1F1 induces cancer stem cell-like traits in breast cancer cells by IL-6/JAK2/STAT3 activation and enrichment of ALDH.NPJ breast cancer · 2026Article
- Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation.Science advances · 2026Article
- Advances in Next-Generation Immunotherapies for Ovarian Cancer: Mechanisms of Immune Evasion and Novel Therapeutic Targets.Biomolecules · 2026Review
- Evaluating the Therapeutic Potential of MRT68921 and Afatinib in Three-Dimensional Models of Epithelial Ovarian Cancer.Cancers · 2026Article
- Dissecting Cancer Metabolism and Therapeutic Resistance Using In Vitro Platforms.Advances in experimental medicine and biology · 2026Review
- ACSS2 promotes proliferation and invasiveness of SKOV-3 and PA-1 ovarian cancer cell lines under hypoxia.Journal of ovarian research · 2025Article
- Double-Blind Randomized Phase 2 Trial Testing Personal Cancer Vaccines in Patients with Advanced Ovarian Cancer.Vaccines · 2025Article
- Harnessing ovarian cancer ascites for translational science: models, biomarkers, and therapeutics.Molecular cancer · 2025Review
- Loss ofOncotarget · 2025Article
- The 3D Language of Cancer: Communication via Extracellular Vesicles from Tumor Spheroids and Organoids.International journal of molecular sciences · 2025Review
- Glucosylceramide Synthase, a Key Enzyme in Sphingolipid Metabolism, Regulates Expression of Genes Accounting for Cancer Drug Resistance.International journal of molecular sciences · 2025Article
- Review
- TIMP1 Overexpression in Ovarian Cancer Spheroids: Implications for Prognosis, Resistance, and Metastatic Potential.Cancers · 2025Article
- Estrogen-related receptor alpha (ERRα) controls the stemness and cellular energetics of prostate cancer cells via its direct regulation of citrate metabolism and zinc transportation.Cell death & disease · 2025Article
- MicroRNA-379-5p attenuates cancer stem cells and reduces cisplatin resistance in ovarian cancer by regulating RAD18/Polη axis.Cell death & disease · 2025Article
170 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >10(5) parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. (13)C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy.
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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.