ArticleBreast cancer research : BCR2018
A novel neuregulin - jagged1 paracrine loop in breast cancer transendothelial migration.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Zhoushi Qiling decoction inhibits neuregulin 1 secreted from cancer-associated fibroblasts to ameliorate enzalutamide resistance in prostate cancer.Journal of traditional and complementary medicine · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.Oncogene · 2025Article
- TFAP2A enhances tumor stemness and promotes metastasis in pancreatic ductal adenocarcinoma.iScience · 2025Article
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- The Brain-Penetrant Pan-ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases.Cancer research · 2025Article
- OX-40 signaling promotes tumorigenesis in CTCL by regulating ERK activation.Frontiers in immunology · 2025Article
- Signaling events at TMEM doorways provide potential targets for inhibiting breast cancer dissemination.bioRxiv : the preprint server for biology · 2024Article
- Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis.bioRxiv : the preprint server for biology · 2024Article
- Cooperative NF-κB and Notch1 signaling promotes macrophage-mediated MenaINV expression in breast cancer.Breast cancer research : BCR · 2023Article
- Gut microbiota: key facilitator in metastasis of colorectal cancer.Frontiers in oncology · 2023Review
- Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance.International journal of molecular sciences · 2022Review
- Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier.International journal of molecular sciences · 2022Article
- Article
- Live tumor imaging shows macrophage induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination.Nature communications · 2021Article
- Review
- Neuregulin in Health and Disease.International journal of brain disorders and treatment · 2018Article
- Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment.Frontiers in immunology · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe interaction of breast cancer cells with other cells in the tumor microenvironment plays an important role in metastasis. Invasion and intravasation, two critical steps in the metastatic process, are influenced by these interactions. Macrophages are of particular interest when it comes to studying tumor cell invasiveness. Previous studies have shown that there is paracrine loop signaling between breast cancer cells and macrophages involving colony stimulating factor 1 (CSF-1) produced by tumor cells and epidermal growth factor (EGF) production by macrophages. In this paper, we identify a novel paracrine loop between tumor cells and macrophages involving neuregulin (NRG1) and notch signaling.
methodsThe aim of this study was to determine the role of NRG1, a ligand of the ErbB3 receptor, in macrophage stimulation of tumor cell transendothelial migration and intravasation. We used fluorescence-activated cell sorting (FACS) and western blot to determine ErbB3 and NRG1 expression, respectively. An in vitro transendothelial migration (iTEM) assay was used to examine the effects of short hairpin (sh)RNA targeting NRG1 in tumor cells and clustered regularly interspaced short palindromic repeats (CRISPR) knockout of jagged 1 (JAG1) in macrophages. Orthotopic xenograft injections in mice were used to confirm results in vivo.
resultsIn our system, macrophages were the primary cells showing expression of ErbB3, and a blocking antibody against ErbB3 resulted in a significant decrease in macrophage-induced transendothelial migration of breast cancer cells. Stimulation of macrophages with NRG1 upregulated mRNA and protein expression of JAG1, a ligand of the Notch receptor, and JAG1 production by macrophages was important for transendothelial migration of tumor cells.
conclusionsThis study demonstrates that stimulation of macrophages by tumor cell NRG1 can enhance transendothelial migration and intravasation. We also demonstrate that this effect is due to induction of macrophage JAG1, an important ligand of the Notch signaling pathway.
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