ArticleJournal of experimental & clinical cancer research : CR2021
Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Reprogramming the Immunosuppressive Microenvironment in Triple-Negative Breast Cancer via FAP-Targeted Nanoprobes for Multimodal Imaging and Photothermal Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Spatial organization of the TNBC tumor microenvironment: multicellular niches, T-cell bottlenecks, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Applications and development of in situ nucleic acid visualization techniques.Frontiers in bioengineering and biotechnology · 2026Review
- Hippo-YAP/TAZ signaling in gastric cancer: orchestrating epithelial-stromal heterogeneity, plasticity, and therapy resistance.Cancer heterogeneity and plasticity · 2026Article
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Cancer associated fibroblasts in cancer development and therapy.Journal of hematology & oncology · 2025Review
- Novel FAP-Targeted Heptamethine Cyanines for NIRF Imaging Applications.Molecular pharmaceutics · 2025Article
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The role of CAFs in therapeutic resistance in triple negative breast cancer: an emerging challenge.Frontiers in molecular biosciences · 2025Review
- Review
- Tumor-associated mesenchymal stromal cells modulate macrophage phagocytosis in stromal-rich colorectal cancer via PD-1 signaling.iScience · 2024Article
- Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy.Cancer metastasis reviews · 2024Review
- Patient-specific colorectal-cancer-associated fibroblasts modulate tumor microenvironment mechanics.iScience · 2024Article
- Cancer-associated fibroblasts: heterogeneity and their role in the tumor immune response.Clinical and experimental medicine · 2024Review
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 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
- Irradiated Mammary Spheroids Elucidate Mechanisms of Macrophage-Mediated Breast Cancer Recurrence.Cellular and molecular bioengineering · 2023Article
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11 authors.
Funding
Abstract
backgroundCancer-associated fibroblasts (CAFs) comprise a heterogeneous population of stromal cells within the tumour microenvironment. CAFs exhibit both tumour-promoting and tumour-suppressing functions, making them exciting targets for improving cancer treatments. Careful isolation, identification, and characterisation of CAF heterogeneity is thus necessary for ex vivo validation and future implementation of CAF-targeted strategies in cancer.
methodsMurine 4T1 (metastatic) and 4T07 (poorly/non-metastatic) orthotopic triple negative breast cancer tumours were collected after 7, 14, or 21 days. The tumours were analysed via flow cytometry for the simultaneous expression of six CAF markers: alpha smooth muscle actin (αSMA), fibroblast activation protein alpha (FAPα), platelet derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ), CD26/DPP4 and podoplanin (PDPN). All non-CAFs were excluded from the analysis using a lineage marker cocktail (CD24, CD31, CD45, CD49f, EpCAM, LYVE-1, and TER-119). In total 128 murine tumours and 12 healthy mammary fat pads were analysed.
resultsWe have developed a multicolour flow cytometry strategy based on exclusion of non-CAFs and successfully employed this to explore the temporal heterogeneity of freshly isolated CAFs in the 4T1 and 4T07 mouse models of triple-negative breast cancer. Analysing 128 murine tumours, we identified 5-6 main CAF populations and numerous minor ones based on the analysis of αSMA, FAPα, PDGFRα, PDGFRβ, CD26, and PDPN. All markers showed temporal changes with a distinct switch from primarily PDGFRα+ fibroblasts in healthy mammary tissue to predominantly PDGFRβ+ CAFs in tumours. CD26+ CAFs emerged as a large novel subpopulation, only matched by FAPα+ CAFs in abundance.
conclusionWe demonstrate that multiple subpopulations of CAFs co-exist in murine triple negative breast cancer, and that the abundance and dynamics for each marker differ depending on tumour type and time. Our results form the foundation needed to isolate and characterise specific CAF populations, and ultimately provide an opportunity to therapeutically target specific CAF subpopulations.
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