ArticleOncotarget2016
Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 124 citations in OpenAlex.
- Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.JCI insight · 2020Trial
- Article
- Mesenchymal stromal/stem cells in tumour initiation, progression and therapy.Nature reviews. Cancer · 2026Review
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- A novel humanized immune stroma PDX cancer model for therapeutic studies.Cancer immunology, immunotherapy : CII · 2026Article
- Critical roles of Hedgehog signaling pathway in regulating the multidrug resistance of ovarian cancer.Journal of ovarian research · 2026Review
- Combination of oxidative phosphorylation and platelet-derived growth factor inhibitors for the treatment of ovarian cancers.npj women's health · 2026Article
- Tumoroid model recreates clinically relevant phenotypes of high grade serous ovarian cancer (HGSC) cells, carcinoma associated fibroblasts, and macrophages.Research square · 2025Article
- Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.Cancer discovery · 2025Article
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- Cracking the code: predicting tumor microenvironment enabled chemoresistance with machine learning in the human tumoroid models.npj biomedical innovations · 2025Article
- Mesenchymal stem cells lineage and their role in disease development.Molecular medicine (Cambridge, Mass.) · 2024Review
- The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions.Cancer cell · 2024Article
- Mesenchymal stromal cells as cancer promoters.Oncogene · 2024Review
- Carcinoma-associated mesenchymal stem cells promote ovarian cancer heterogeneity and metastasis through mitochondrial transfer.Cell reports · 2024Article
- Bone Marrow Mesenchymal Stem Cells Promote Ovarian Cancer Cell Proliferation via Cytokine Interactions.International journal of molecular sciences · 2024Article
- Mesenchymal Stem Cells Increase Drug Tolerance of A431 Cells Only in 3D Spheroids, Not in 2D Co-Cultures.International journal of molecular sciences · 2024Article
- Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.Communications biology · 2024Article
- Co-Delivery Polymeric Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles to Target Cancer Stem-Like Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Stromal-Modulated Epithelial-to-Mesenchymal Transition in Cancer Cells.Biomolecules · 2023Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The tumor microenvironment is critical to cancer growth and therapy resistance. We previously characterized human ovarian carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are multi-potent cells that can differentiate into tumor microenvironment components including fibroblasts, myofibroblasts and adipocytes. We previously reported CA-MSCs, compared to normal MSCs, express high levels of BMP proteins and promote tumor growth by increasing numbers of cancer stem-like cells (CSCs). We demonstrate here that ovarian tumor cell-secreted Hedgehog (HH) induces CA-MSC BMP4 expression. CA-MSC-derived BMP4 reciprocally increases ovarian tumor cell HH expression indicating a positive feedback loop. Interruption of this loop with a HH pathway inhibitor or BMP4 blocking antibody decreases CA-MSC-derived BMP4 and tumor-derived HH preventing enrichment of CSCs and reversing chemotherapy resistance. The impact of HH inhibition was only seen in CA-MSC-containing tumors, indicating the importance of a humanized stroma. These results are reciprocal to findings in pancreatic and bladder cancer, suggesting HH signaling effects are tumor tissue specific warranting careful investigation in each tumor type. Collectively, we define a critical positive feedback loop between CA-MSC-derived BMP4 and ovarian tumor cell-secreted HH and present evidence for the further investigation of HH as a clinical 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.