ArticleProceedings of the National Academy of Sciences of the United States of America2015
Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.JCI insight · 2020Trial
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- Single-Cell RNA Sequencing Identifies MMP11Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumoroid model recreates clinically relevant phenotypes of high grade serous ovarian cancer (HGSC) cells, carcinoma associated fibroblasts, and macrophages.Research square · 2025Article
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Role of cancer stem cell heterogeneity in intrahepatic cholangiocarcinoma.Translational cancer research · 2025Article
- Article
- Comparative Analysis of Primary Ovarian Cancer Cells and Established Cell Lines as a New Tool for Studies on Ovarian Cancer Cell Complexity.International journal of molecular sciences · 2024Article
- Applications of Innovation Technologies for Personalized Cancer Medicine: Stem Cells and Gene-Editing Tools.ACS pharmacology & translational science · 2023Review
- BMP signaling in cancer stemness and differentiation.Cell regeneration (London, England) · 2023Review
- A putative role for ALDH inhibitors and chemoprevention of BRCA-mutation-driven tumors.Gynecologic oncology · 2023Article
- Quiescent Ovarian Cancer Cells Secrete Follistatin to Induce Chemotherapy Resistance in Surrounding Cells in Response to Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeting ovarian cancer stem cells: a new way out.Stem cell research & therapy · 2023Review
- Targeting Therapeutic Resistance and Multinucleate Giant Cells in CCNE1-Amplified HR-Proficient Ovarian Cancer.Molecular cancer therapeutics · 2022Article
- Revisiting chemoresistance in ovarian cancer: Mechanism, biomarkers, and precision medicine.Genes & diseases · 2022Review
- 3D and organoid culture in research: physiology, hereditary genetic diseases and cancer.Cell & bioscience · 2022Review
- Cancer Stem Cells in Ovarian Cancer-A Source of Tumor Success and a Challenging Target for Novel Therapies.International journal of molecular sciences · 2022Review
- Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.Acta biomaterialia · 2021Review
- MicroRNA-378a-3p is overexpressed in psoriasis and modulates cell cycle arrest in keratinocytes via targeting BMP2 gene.Scientific reports · 2021Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Whether human cancer follows a hierarchical or stochastic model of differentiation is controversial. Furthermore, the factors that regulate cancer stem-like cell (CSC) differentiation potential are largely unknown. We used a novel microfluidic single-cell culture method to directly observe the differentiation capacity of four heterogeneous ovarian cancer cell populations defined by the expression of the CSC markers aldehyde dehydrogenase (ALDH) and CD133. We evaluated 3,692 progeny from 2,833 cells. We found that only ALDH(+)CD133(+) cells could generate all four ALDH(+/-)CD133(+/-) cell populations and identified a clear branched differentiation hierarchy. We also observed a single putative stochastic event. Within the hierarchy of cells, bone morphologenetic protein 2 (BMP2) is preferentially expressed in ALDH(-)CD133(-) cells. BMP2 promotes ALDH(+)CD133(+) cell expansion while suppressing the proliferation of ALDH(-)CD133(-) cells. As such, BMP2 suppressed bulk cancer cell growth in vitro but increased tumor initiation rates, tumor growth, and chemotherapy resistance in vivo whereas BMP2 knockdown reduced CSC numbers, in vivo growth, and chemoresistance. These data suggest a hierarchical differentiation pattern in which BMP2 acts as a feedback mechanism promoting ovarian CSC expansion and suppressing progenitor proliferation. These results explain why BMP2 suppresses growth in vitro and promotes growth in vivo. Together, our results support BMP2 as a therapeutic target in ovarian cancer.
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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.