ArticleOncotarget2016
Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Mammary Fibroblasts Secrete Damage Associated Molecular Patterns Through Extracellular Vesicles in Response to Ionizing Radiation.Journal of extracellular biology · 2026Article
- MLK4 orchestrates macrophage-induced triple-negative breast cancer invasion and ECM remodeling via enhanced paracrine signaling and NF-κB-MMP axis activation.Cell death & disease · 2026Article
- Article
- Uncovering Cellular Interactome Drivers of Immune Checkpoint Inhibitor Response in Advanced Melanoma Patients.Cellular and molecular bioengineering · 2025Article
- Article
- Reduced JAG1 Expression Through miR-200 Overexpression or Crispr-Cas Mediated Knockout Impairs TNBC Growth and Metastasis.Molecular carcinogenesis · 2025Article
- Redefining macrophage phenotypes after spinal cord injury: An open data approach.Experimental neurology · 2025Article
- Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors-a network meta-analysis.Frontiers in immunology · 2025Article
- SerpinE2 promotes M2 polarization in macrophage to accelerate colorectal cancer progression.Frontiers in oncology · 2025Article
- CREB-binding protein/P300 bromodomain inhibition reduces neutrophil accumulation and activates antitumor immunity in triple-negative breast cancer.JCI insight · 2024Article
- CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC.bioRxiv : the preprint server for biology · 2024Article
- Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia.Cell death discovery · 2024Article
- Serpin peptidase inhibitor, clade E, member 2 in physiology and pathology: recent advancements.Frontiers in molecular biosciences · 2024Review
- Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- [Oral Squamous Cell Carcinoma-Derived Cell-Free DNA Modulates Stemness and Migration of Oral Squamous Cell Carcinoma Cell Line by Inducing M2 Macrophage Polarization].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.Journal of experimental & clinical cancer research : CR · 2023Article
- Single-cell RNA-seq integrated with multi-omics reveals SERPINE2 as a target for metastasis in advanced renal cell carcinoma.Cell death & disease · 2023Article
- Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses.Biomedicines · 2023Article
- Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma.Cancer discovery · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that serpinE2 creates tumor-promoting conditions in the tumor microenvironment (TME) by affecting extracellular matrix remodeling. Using two different breast cancer models, we show that blocking serpinE2, either by knock-down (KD) in tumor cells or in response to a serpinE2 binding antibody, decreases metastatic dissemination from primary tumors to the lungs. We demonstrate that in response to serpinE2 KD or antibody treatment there are dramatic changes in the TME. Multiphoton intravital imaging revealed deposition of a dense extracellular collagen I matrix encapsulating serpinE2 KD or antibody-treated tumors. This is accompanied by a reduction in the population of tumor-promoting macrophages, as well as a decrease in chemokine ligand 2, which is known to affect macrophage abundance and polarization. In addition, TIMP-1 secretion is increased, which may directly inhibit matrix metalloproteases critical for collagen degradation in the tumor. In summary, our findings suggest that serpinE2 is required in the extracellular milieu of tumors where it acts in multiple ways to regulate tumor matrix deposition, thereby controlling tumor cell dissemination.
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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.