ArticleBreast cancer research : BCR2012
Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 66 citations in OpenAlex.
- Trial
- Metabolic programming defines oxygen-sensitive subpopulation hierarchies and patterning in collective invasion.Molecular biology of the cell · 2025Article
- Visualizing cellular interactions: intravital imaging in tumor microenvironment.Frontiers in immunology · 2025Review
- Review
- Dynamic EMT: a multi-tool for tumor progression.The EMBO journal · 2021Review
- Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression.British journal of cancer · 2021Review
- Plasticity of cancer cell invasion: Patterns and mechanisms.Translational oncology · 2021Review
- P120 Catenin Isoforms Differentially Associate with Breast Cancer Invasion and Metastasis.Cancers · 2019Article
- Traction microscopy with integrated microfluidics: responses of the multi-cellular island to gradients of HGF.Lab on a chip · 2019Article
- Detection of epigenetic field defects using a weighted epigenetic distance-based method.Nucleic acids research · 2019Article
- Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.Cellular & molecular biology letters · 2019Article
- Role of Transglutaminase 2 in Migration of Tumor Cells and How Mouse Models Fit.Medical sciences (Basel, Switzerland) · 2018Review
- From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β.Scientific reports · 2018Article
- Intravital microscopy in the study of the tumor microenvironment: from bench to human application.Oncotarget · 2018Review
- Reduced SMAD2/3 activation independently predicts increased depth of human cutaneous squamous cell carcinoma.Oncotarget · 2018Article
- Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis.Scientific reports · 2018Article
- Zearalenone Exposure Enhanced the Expression of Tumorigenesis Genes in Donkey Granulosa Cells via theFrontiers in genetics · 2018Article
- The CAM cancer xenograft as a model for initial evaluation of MR labelled compounds.Scientific reports · 2017Article
- Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis.Scientific reports · 2017Article
- Progression of chronic kidney disease: too much cellular talk causes damage.Kidney international · 2017Review
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10 authors at 2 institutions in 1 country.
Funding
Abstract
introductionTransforming growth factor beta (TGF-β) has a dual role during tumor progression, initially as a suppressor and then as a promoter. Epithelial TGF-β signaling regulates fibroblast recruitment and activation. Concurrently, TGF-β signaling in stromal fibroblasts suppresses tumorigenesis in adjacent epithelia, while its ablation potentiates tumor formation. Much is known about the contribution of TGF-β signaling to tumorigenesis, yet the role of TGF-β in epithelial-stromal migration during tumor progression is poorly understood. We hypothesize that TGF-β is a critical regulator of tumor-stromal interactions that promote mammary tumor cell migration and invasion.
methodsFluorescently labeled murine mammary carcinoma cells, isolated from either MMTV-PyVmT transforming growth factor-beta receptor II knockout (TβRII KO) or TβRIIfl/fl control mice, were combined with mammary fibroblasts and xenografted onto the chicken embryo chorioallantoic membrane. These combinatorial xenografts were used as a model to study epithelial-stromal crosstalk. Intravital imaging of migration was monitored ex ovo, and metastasis was investigated in ovo. Epithelial RNA from in ovo tumors was isolated by laser capture microdissection and analyzed to identify gene expression changes in response to TGF-β signaling loss.
resultsIntravital microscopy of xenografts revealed that mammary fibroblasts promoted two migratory phenotypes dependent on epithelial TGF-β signaling: single cell/strand migration or collective migration. At epithelial-stromal boundaries, single cell/strand migration of TβRIIfl/fl carcinoma cells was characterized by expression of α-smooth muscle actin and vimentin, while collective migration of TβRII KO carcinoma cells was identified by E-cadherin+/p120+/β-catenin+ clusters. TβRII KO tumors also exhibited a twofold greater metastasis than TβRIIfl/fl tumors, attributed to enhanced extravasation ability. In TβRII KO tumor epithelium compared with TβRIIfl/fl epithelium, Igfbp4 and Tspan13 expression was upregulated while Col1α2, Bmp7, Gng11, Vcan, Tmeff1, and Dsc2 expression was downregulated. Immunoblotting and quantitative PCR analyses on cultured cells validated these targets and correlated Tmeff1 expression with disease progression of TGF-β-insensitive mammary cancer.
conclusionFibroblast-stimulated carcinoma cells utilize TGF-β signaling to drive single cell/strand migration but migrate collectively in the absence of TGF-β signaling. These migration patterns involve the signaling regulation of several epithelial-to-mesenchymal transition pathways. Our findings concerning TGF-β signaling in epithelial-stromal interactions are important in identifying migratory mechanisms that can be targeted as recourse for breast cancer treatment.
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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.