ArticleOncotarget2018
Three-dimensional tumor model mimics stromal - breast cancer cells signaling.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- A CXCR4/PD-L1 Bispecific Nanobody Engineered for Tumor Microenvironment Retention Mediates Sustained Synergy with Chemotherapy via Remodeling Immunity in TNBC.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- A gravity-driven tissue chip to study the efficacy and toxicity of cancer therapeutics.Lab on a chip · 2024Article
- Three-Dimensional Tumor Models to Study Cancer Stemness-Mediated Drug Resistance.Cellular and molecular bioengineering · 2024Review
- A ten long noncoding RNA-based prognostic risk model construction and mechanism study in the basal-like immune-suppressed subtype of triple-negative breast cancer.Translational cancer research · 2023Article
- Article
- Inhibiting BRAF/EGFR/MEK suppresses cancer stemness and drug resistance of primary colorectal cancer cells.Oncotarget · 2023Article
- Polyglycerol-Based Biomedical Matrix for Immunomagnetic Circulating Tumor Cell Isolation and Their Expansion into Tumor Spheroids for Drug Screening.Advanced healthcare materials · 2023Article
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Inclusion of cancer-associated fibroblasts in drug screening assays to evaluate pancreatic cancer resistance to therapeutic drugs.Journal of physiology and biochemistry · 2023Article
- The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity.Frontiers in oncology · 2023Review
- Therapeutic Targeting of Stromal-Tumor HGF-MET Signaling in an Organotypic Triple-Negative Breast Tumor Model.Molecular cancer research : MCR · 2022Article
- Optical tissue clearing associated with 3D imaging: application in preclinical and clinical studies.Histochemistry and cell biology · 2022Review
- Strategies for developing complex multi-component in vitro tumor models: Highlights in glioblastoma.Advanced drug delivery reviews · 2022Review
- Chemokine signaling in cancer-stroma communications.Journal of cell communication and signaling · 2021Review
- Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes.PloS one · 2021Article
- Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies.Frontiers in oncology · 2021Review
- Gaining New Biological and Therapeutic Applications into the Liver with 3D In Vitro Liver Models.Tissue engineering and regenerative medicine · 2020Review
- Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks.Journal of mammary gland biology and neoplasia · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor stroma is a major contributor to the biological aggressiveness of cancer cells. Cancer cells induce activation of normal fibroblasts to carcinoma-associated fibroblasts (CAFs), which promote survival, proliferation, metastasis, and drug resistance of cancer cells. A better understanding of these interactions could lead to new, targeted therapies for cancers with limited treatment options, such as triple negative breast cancer (TNBC). To overcome limitations of standard monolayer cell cultures and xenograft models that lack tumor complexity and/or human stroma, we have developed a high throughput tumor spheroid technology utilizing a polymeric aqueous two-phase system to conveniently model interactions of CAFs and TNBC cells and quantify effects on signaling and drug resistance of cancer cells. We focused on signaling by chemokine CXCL12, a hallmark molecule secreted by CAFs, and receptor CXCR4, a driver of tumor progression and metastasis in TNBC. Using three-dimensional stromal-TNBC cells cultures, we demonstrate that CXCL12 - CXCR4 signaling significantly increases growth of TNBC cells and drug resistance through activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. Despite resistance to standard chemotherapy, upregulation of MAPK and PI3K signaling sensitizes TNBC cells in co-culture spheroids to specific inhibitors of these kinase pathways. Furthermore, disrupting CXCL12 - CXCR4 signaling diminishes drug resistance of TNBC cells in co-culture spheroid models. This work illustrates the capability to identify mechanisms of drug resistance and overcome them using our engineered model of tumor-stromal interactions.
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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.