ArticleJournal of translational medicine2015
Expression of cancer-associated fibroblast related proteins in metastatic breast cancer: an immunohistochemical analysis.
Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Predicting fibroblast activation protein overexpression in the overall survival rate of cancer patients: a systematic review and meta-analysis.Systematic reviews · 2025Pooled it
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Prospective comparison of [European journal of nuclear medicine and molecular imaging · 2026Trial
- Clinical utilities of platelet-derived growth factor signaling in breast cancer.Pharmacological research · 2026Review
- Exploring Morphology of Thermoplasmonic Nanoparticles to Synergize Immunotherapeutic Fibroblast Activation Protein-Positive Cell Sensitization and Photothermal Therapy.Small science · 2025Article
- Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC).Journal of translational medicine · 2025Article
- The role of CAFs in therapeutic resistance in triple negative breast cancer: an emerging challenge.Frontiers in molecular biosciences · 2025Review
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Artificial intelligence: illuminating the depths of the tumor microenvironment.Journal of translational medicine · 2024Review
- Heterogeneity of primary and metastatic CAFs: From differential treatment outcomes to treatment opportunities (Review).International journal of oncology · 2024Article
- Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.Journal of translational medicine · 2023Review
- Analysis of stromal PDGFR-β and α-SMA expression and their clinical relevance in brain metastases of breast cancer patients.BMC cancer · 2023Article
- Identification of Cancer-Associated Fibroblasts in Metastatic Lymph Nodes of Colorectal Carcinoma.Bulletin of experimental biology and medicine · 2023Article
- The role of cancer-associated fibroblasts in breast cancer metastasis.Frontiers in oncology · 2023Review
- What is the Potential Interplay between Microbiome and Tumor Microenvironment in Oral Squamous Cell Carcinomas?Asian Pacific journal of cancer prevention : APJCP · 2022Review
- Metformin counteracts stimulatory effects induced by insulin in primary breast cancer cells.Journal of translational medicine · 2022Article
- Cancer-associated fibroblasts in breast cancer: Challenges and opportunities.Cancer communications (London, England) · 2022Review
- GLIS1 in Cancer-Associated Fibroblasts Regulates the Migration and Invasion of Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Invasive Breast Carcinoma with Abundant Collagenous Stroma Shows Lower Level of CD68-Positive Tumor Associated Macrophages than Those of Invasive Carcinoma without Abundant Collagenous Stroma.Acta bio-medica : Atenei Parmensis · 2021Article
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3 authors at 2 institutions in 1 country.
Funding
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Abstract
backgroundCancer-associated fibroblast (CAF) is the most studied element of the tumor microenvironment, although no relationship has been identified between expression of their related proteins and the metastasis site. The purpose of this study was to investigate the expression of CAF related proteins and their implications according to the metastasis site in metastatic breast cancer.
methodsImmunohistochemical staining was used to evaluate the expression of CAF related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFRα, PDGFRβ, and NG2) in tissue microarrays from 132 cases of metastatic breast cancer (bone metastasis: 32 cases, brain metastasis: 38 cases, liver metastasis: 10 cases, and lung metastasis: 52 cases). Breast cancer subtypes were classified as luminal A, luminal B, HER-2, and triple negative breast cancer, according to the immunohistochemical staining results for estrogen and progesterone receptors, HER-2, and Ki-67 and FISH results for HER-2. Tumors were classified as desmoplastic, sclerotic, normal-like, and inflammatory type, according to the histologic findings from the tumor stroma.
resultsVarious CAF related protein expression profiles were observed, according to the metastasis site. For bone metastasis, the expression of stromal podoplanin, S100A4, and PDGFRα was significantly high. For lung metastasis, the expression of stromal PDGFRβ was significantly elevated (p < 0.001). For liver metastasis, significantly reduced expression of stromal S100A4 (p = 0.002) and PDGFRα (p = 0.011) was observed. Expression of CAF related proteins also differed according to the stromal phenotype. Desmoplastic stroma exhibited significantly elevated expression of stromal podoplanin (p < 0.001), S100A4 (p < 0.001), PDGFRα (p = 0.010), and PDGFRβ (p = 0.021). Inflammatory stroma exhibited significantly elevated expression of stromal FAPα (p = 0.044) and significantly reduced stromal S100A4 expression (p < 0.001). Sclerotic stroma exhibited significantly elevated tumoral FAPα (p = 0.005) expression. For lung metastasis, shorter overall survival was significantly related to tumoral podoplanin expression (p = 0.006), stromal podoplanin expression (p = 0.018), tumoral prolyl 4-hydroxylase negativity (p = 0.016), and tumoral PDGFRα expression (p = 0.001).
conclusionFor metastatic breast cancer, significant differences were observed in the expression of CAF related proteins, according to the metastasis site and stromal histologic phenotype.
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