ArticleProceedings of the National Academy of Sciences of the United States of America2012
Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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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.
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Who cites it
76 citing papers in PubMed, 119 citations in OpenAlex.
- Ascites analysis by a microfluidic chip allows tumor-cell profiling.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer.The Journal of biological chemistry · 2012Trial
- Cell Fusion and Syncytia Formation in Cancer.Results and problems in cell differentiation · 2024Review
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Tumor-associated macrophages induce inflammation and drug resistance in a mechanically tunable engineered model of osteosarcoma.Biomaterials · 2023Article
- Tumor microenvironment-induced tumor cell plasticity: relationship with hypoxic stress and impact on tumor resistance.Frontiers in oncology · 2023Review
- Article
- Cancer Stem Cells in Ovarian Cancer-A Source of Tumor Success and a Challenging Target for Novel Therapies.International journal of molecular sciences · 2022Review
- Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer.World journal of surgical oncology · 2022Article
- Ovarian cancer stem cells: Critical roles in anti-tumor immunity.Frontiers in genetics · 2022Review
- Resetting the epigenome: Methylation dynamics in cancer stem cells.Frontiers in cell and developmental biology · 2022Review
- Photodynamic Treatments for Disseminated Cancer Metastases Using Fiber-Optic Technologies.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Anti-Müllerian hormone concentration regulates activin receptor-like kinase-2/3 expression levels with opposing effects on ovarian cancer cell survival.International journal of oncology · 2021Article
- Article
- The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells.Scientific reports · 2021Article
- GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells.Bone & joint research · 2021Article
- Article
- Anti-Müllerian hormone (AMH) autocrine signaling promotes survival and proliferation of ovarian cancer cells.Scientific reports · 2021Article
- Article
16 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
Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.
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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.