ArticleOncogenesis2018
Neutrophil TLR4 and PKR are targets of breast cancer cell glycosaminoglycans and effectors of glycosaminoglycan-induced APRIL secretion.
Article in Oncogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Neutrophils matter: new clinical insights on their role in the progression of metastatic breast cancer.Breast cancer research : BCR · 2025Article
- Sulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP.Cancer biology & therapy · 2025Article
- Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer.Cell reports. Medicine · 2025Article
- Identification of tumor associated neutrophils-related genes in triple-negative breast cancer for predicting prognosis and therapeutic response through integrated single-cell analysis.Frontiers in immunology · 2025Article
- Tumor-associated neutrophils in breast cancer: an angel or a devil?Frontiers in immunology · 2025Review
- The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.Breast cancer research : BCR · 2024Article
- Neutrophil depletion attenuates antibody-mediated rejection in a renal transplantation mouse model.Clinical and experimental immunology · 2024Article
- Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay.Frontiers in pharmacology · 2024Article
- A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.International journal of molecular sciences · 2023Article
- Anti‑βInternational journal of molecular medicine · 2022Article
- Pretreatment with Propofol Reduces Pulmonary Injury in a Pig Model of Intestinal Ischemia-Reperfusion via Suppressing the High-Mobility Group Box 1 Protein (HMGB1)/Toll-Like Receptor 4 (TLR4)/Protein Kinase R (PKR) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Identification and validation of a novel ferroptosis-related gene model for predicting the prognosis of gastric cancer patients.PloS one · 2021Article
- A Proliferation-Inducing Ligand Regulation in Polymorphonuclear Neutrophils by Panax ginseng.Archivum immunologiae et therapiae experimentalis · 2020Article
- Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression.International journal of molecular sciences · 2020Review
- Upregulated hsa_circ_0005785 Facilitates Cell Growth and Metastasis of Hepatocellular Carcinoma Through the miR-578/APRIL Axis.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A proliferation-inducing ligand (APRIL), which induces survival and migration signals and tumor growth, is commonly observed in breast cancer tissues but is not often expressed in breast cancer cells themselves. Here, we examined whether breast cancer cells induce APRIL secretion from neutrophils, which are frequently recruited into the breast tumor microenvironment. We found that breast cancer cells do stimulate neutrophils to secrete APRIL through their glycosaminoglycans. Breast cancer cells depleted of heparan sulfate or chondroitin sulfate glycosaminoglycans lose their ability to induce APRIL secretion from neutrophils, and heparan sulfate and chondroitin sulfate can induce secretion that is comparable to that of breast cancer cell-induced secretion. While stimulation of the RNA-activated protein kinase (PKR) is sufficient to induce neutrophil APRIL secretion, both PKR and the toll-like receptor 4 (TLR4) are required for breast cancer cell glycosaminoglycan-induced secretion as separate and specific inhibition of TLR4 or PKR completely prevents the process, suggesting that breast cancer cell glycosaminoglycans target neutrophil TLR4 and PKR to trigger APRIL secretion. Thus, apart from the putative role of cell surface heparan sulfate in binding APRIL that leads to cell growth, we demonstrate that heparan sulfate, as well as chondroitin sulfate plays a novel role in promoting neutrophil secretion of APRIL that could lead to further cell growth. We propose that breast cancer cells take advantage of the neutrophil recruitment to the tumor microenvironment through the dual role of heparan sulfate as cell surface receptor or docking molecule for APRIL and as a ligand that induces neutrophil APRIL secretion to promote their own growth.
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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.