ArticleThe Journal of clinical investigation1995
The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 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.
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Who cites it
175 citing papers in PubMed, 445 citations in OpenAlex.
- FAM177A1 disrupts SIRT3-SOD2 signaling to drive mitochondrial dysfunction-mediated VSMC phenotypic switching in vascular remodeling.International journal of biological sciences · 2026Article
- Fibroblast transformation in the tumor microenvironment of lung adenocarcinoma: heterogeneity, regulation, and therapeutic targeting.Frontiers in immunology · 2026Review
- Empowering hypoxia to convert cold tumors into hot tumors for breast cancer immunotherapy.Cell death discovery · 2025Review
- CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway.Biology direct · 2025Article
- Breast Morphogenesis: From Normal Development to Cancer.Advances in experimental medicine and biology · 2025Review
- 3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity.Bioactive materials · 2024Article
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- The impact of tumor microenvironment: unraveling the role of physical cues in breast cancer progression.Cancer metastasis reviews · 2024Review
- Evidence of steady-state fibroblast subtypes in the normal human breast as cells-of-origin for perturbed-state fibroblasts in breast cancer.Breast cancer research : BCR · 2024Article
- Exploring the multifaceted role of direct interaction between cancer cells and fibroblasts in cancer progression.Frontiers in molecular biosciences · 2024Review
- Breast pericytes: a newly identified driver of tumor cell proliferation.Frontiers in oncology · 2024Article
- The Influence of Betulin Derivatives EB5 and ECH147 on the Expression of Selected TGFβ Superfamily Genes,Current issues in molecular biology · 2023Article
- Review
- Article
- CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer.Nature communications · 2023Article
- The role of cancer-associated fibroblasts in breast cancer metastasis.Frontiers in oncology · 2023Review
- Crosstalk between colorectal cancer cells and cancer-associated fibroblasts in the tumor microenvironment mediated by exosomal noncoding RNAs.Frontiers in immunology · 2023Review
- Stem cells for organoids.Smart medicine · 2022Review
- Cellular Plasticity and Heterotypic Interactions during Breast Morphogenesis and Cancer Initiation.Cancers · 2022Review
- Regulation of Tumor Invasion by the Physical Microenvironment: Lessons from Breast and Brain Cancer.Annual review of biomedical engineering · 2022Review
115 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
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The origin of myofibroblasts in stromal reaction has been a subject of controversy. To address this question definitively, we developed techniques for purification and characterization of major stromal cell types. We defined a panel of markers that could, in combination, unequivocally distinguish these cell types by immunocytochemistry, iso-electric focusing, immunoblotting, and two-dimensional gel electrophoresis. We then devised an assay to recapitulate in culture, within two weeks of incubation, critical aspects of the microenvironment in vivo including the typical tissue histology and stromal reaction. When confronted with tumor cells in this assay, fibroblasts readily converted into a graded pattern of myogenic differentiation, strongest in the immediate vicinity of tumor cells. Vascular smooth muscle cells (VSMC), in contrast, did not change appreciably and remained coordinately smooth muscle differentiated. Midcapillary pericytes showed only a slight propensity for myogenic differentiation. Analysis of ten primary tumors implicated converted fibroblasts (10/10), vascular smooth muscle cells (4/10), and pericytes (1/10) in the stromal reaction. Tumor cells were shown to specifically denude the venules both in culture and in vivo, explaining the VSMC phenotype in the stroma. The establishment of this assay and clarification of the origin of these cells pave the way for further analysis of the mechanisms of conversion, and of the consequence of such heterogeneity for diagnosis and 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.