ArticleCell communication and signaling : CCS2018
Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Article
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- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
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- Breast neoplasm epithelial-mesenchymal transition and cytokines: a systematic review.Cancer cell international · 2025Review
- Macrophage regulation of tumor cell dormancy and the dormant niche: an overview in solid tumors.Cancer metastasis reviews · 2025Review
- Osteoclast-derived arachidonic acid triggers dormant lung adenocarcinoma cell activation.iScience · 2025Article
- hsa-mir-483-3p modulates delayed breast cancer recurrence.Scientific reports · 2025Article
- Cell-cell interactions mediating primary and metastatic breast cancer dormancy.Cancer metastasis reviews · 2024Review
- Unveiling cancer dormancy: Intrinsic mechanisms and extrinsic forces.Cancer letters · 2024Review
- The Tumor Immune Microenvironment in Breast Cancer Progression.Acta oncologica (Stockholm, Sweden) · 2024Review
- Outlook and opportunities for engineered environments of breast cancer dormancy.Science advances · 2024Review
- FGFR1 Signaling Facilitates Obesity-Driven Pulmonary Outgrowth in Metastatic Breast Cancer.Molecular cancer research : MCR · 2024Article
- Revealing role of epigenetic modifiers and DNA oxidation in cell-autonomous regulation of Cancer stem cells.Cell communication and signaling : CCS · 2024Article
- Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.Clinical and translational medicine · 2024Review
- Onco-Breastomics: An Eco-Evo-Devo Holistic Approach.International journal of molecular sciences · 2024Review
- Bone Marrow Stroma Co-cultivation Model of Breast Cancer Dormancy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy.Cancer metastasis reviews · 2023Review
- Review
- Dimerization of Transmembrane Proteins in Cancer Immunotherapy.Membranes · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDormant estrogen receptor positive (ER+) breast cancer micrometastases in the bone marrow survive adjuvant chemotherapy and recur stochastically for more than 20 years. We hypothesized that inflammatory cytokines produced by stromal injury can re-awaken dormant breast cancer cells.
methodsWe used an established in vitro dormancy model of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells incubated at clonogenic density on fibronectin-coated plates to determine the effects of inflammatory cytokines on reactivation of dormant ER+ breast cancer cells. We measured induction of a mesenchymal phenotype, motility and the capacity to re-enter dormancy. We induced secretory senescence in murine stromal monolayers by oxidation, hypoxia and estrogen deprivation with hydrogen peroxide (H
resultsExogenous recombinant human (rh) interleukin (IL)-6, IL-8 or transforming growth factor β1 (TGFβ1) induced regrowth of dormant MCF-7 cells on fibronectin-coated plates. Dormant cells had decreased expression of E-cadherin and estrogen receptor α (ERα) and increased expression of N-cadherin and SNAI2 (SLUG). Cytokine or TGFβ1 treatment of dormant clones induced formation of growing clones, a mesenchymal appearance, increased motility and an impaired capacity to re-enter dormancy. Stromal injury induced secretion of IL-6, IL-8, upregulated tumor necrosis factor alpha (TNFα), activated TGFβ and stimulated the growth of co-cultivated MCF-7 cells. MCF-7 cells induced secretion of IL-6 and IL-8 by stroma in co-culture.
conclusionsDormant ER+ breast cancer cells have activated epithelial mesenchymal transition (EMT) gene expression programs and downregulated ERα but maintain a dormant epithelial phenotype. Stromal inflammation reactivates these cells, induces growth and a mesenchymal phenotype. Reactivated, growing cells have an impaired ability to re-enter dormancy. In turn, breast cancer cells co-cultured with stroma induce secretion of IL-6 and IL-8 by the stroma, creating a positive feedback loop.
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