ArticleThe Journal of experimental medicine2023
Pleiotrophin drives a prometastatic immune niche in breast cancer.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 17 citations in OpenAlex.
- Multi-omics profiling identifies CDK1 as a key mediator of mitosis through the PTN pathway in bladder cancer.Future science OA · 2026Article
- Spatial ecology of breast cancer reveals co-evolution of proliferative and dormant niches.Genome medicine · 2026Article
- Pleiotrophin in Mammary Gland Development and Breast Cancer: A Comprehensive Review of the Evidence.Cells · 2026Review
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Common Signatures of Altered Gene Regulation and Invasiveness of Different Breast Cancer Cell Lines after Matrix Interface Crossing.Advanced healthcare materials · 2026Article
- FOXA1 loss drives basal/squamous de-differentiation of prostate cancer and induces an immunosuppressive tumor microenvironment.Nature communications · 2026Article
- Article
- Single-cell analysis reveals that MXRA8 affected the progression of breast cancer via regulating ferroptosis.Cancer cell international · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance.Frontiers in immunology · 2026Article
- The therapeutic effect and specific mechanism involved active Chinese medicine component biochaninA in glioma.Frontiers in immunology · 2026Article
- Single-Cell Sequencing Reveals Novel Tumor Populations and Their Interplay with the Immune Microenvironment in a Pleomorphic Rhabdomyosarcoma.International journal of molecular sciences · 2025Article
- Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial-mesenchymal transition.European journal of medical research · 2025Article
- CD44British journal of cancer · 2025Article
- Tenacissoside G reverses paclitaxel resistance by inhibiting Src/PTN/P-gp signaling axis activation in ovarian cancer cells.Journal of natural medicines · 2025Article
- Decorin as a key marker of desmoplastic cancer-associated fibroblasts mediating first-line immune checkpoint blockade resistance in metastatic gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.Cancer research · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Pleiotrophin serum level and metastasis occurrence in breast cancer patients.Breast disease · 2024Observational
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Metastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-κB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment, and an immune suppressive microenvironment. Consequently, inhibition of PTN, pharmacologically or genetically, reduces the accumulation of tumor-associated neutrophils and reverts local immune suppression, resulting in increased T cell activation and attenuated metastasis. Furthermore, inhibition of PTN significantly enhanced the efficacy of immune checkpoint blockade and chemotherapy in reducing metastatic burden in mice. These findings establish PTN as a previously unrecognized driver of a prometastatic immune niche and thus represents a promising therapeutic target for the treatment of metastatic breast cancer.
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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.