ArticleOncotarget2017
Osteotropism of neuroendocrine tumors: role of the CXCL12/ CXCR4 pathway in promoting EMT in vitro.
Article in Oncotarget, 2017. 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, 28 citations in OpenAlex.
- Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Potential of C-X-C-Chemokine-Receptor-Type-4-Directed PET/CT Using [¹⁸F]AlF-NOTA-QHY-04 in Identifying Molecular Subtypes of Small Cell Lung Cancer.Korean journal of radiology · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Review
- Role of Selected Circulating Tumor Biomarkers in Patients with Skeletal Metastatic Pancreatic Neuroendocrine Neoplasms.Journal of clinical medicine · 2023Article
- Risk Stratification of Pancreatic Neuroendocrine Neoplasms Based on Clinical, Pathological, and Molecular Characteristics.Journal of clinical medicine · 2022Review
- Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors.Journal for immunotherapy of cancer · 2022Article
- Neuroendocrine neoplasia and bone (Review).Experimental and therapeutic medicine · 2021Review
- Wnt/β-Catenin Signaling Regulates CXCR4 Expression and [Diagnostics (Basel, Switzerland) · 2021Article
- Application of "omics" sciences to the prediction of bone metastases from breast cancer: State of the art.Journal of bone oncology · 2021Review
- Pulmonary Neuroendocrine Neoplasms Overexpressing Epithelial-Mesenchymal Transition Mechanical Barriers Genes Lack Immune-Suppressive Response and Present an Increased Risk of Metastasis.Frontiers in oncology · 2021Article
- Molecular mediators of peritoneal metastasis in pancreatic cancer.Cancer metastasis reviews · 2020Review
- Role of Bone Targeting Agents in the Prevention of Bone Metastases from Breast Cancer.International journal of molecular sciences · 2020Review
- Clinical Epigenetics of Neuroendocrine Tumors: The Road Ahead.Frontiers in endocrinology · 2020Review
- Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management.Cancers · 2019Review
- CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC.Cancer research · 2019Article
- Clinical applications of (epi)genetics in gastroenteropancreatic neuroendocrine neoplasms: Moving towards liquid biopsies.Reviews in endocrine & metabolic disorders · 2019Review
- Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours.British journal of cancer · 2019Article
- Macrophage migration inhibitory factor promotes vasculogenic mimicry formation induced by hypoxia via CXCR4/AKT/EMT pathway in human glioblastoma cells.Oncotarget · 2017Article
- pIL6-TRAIL-engineered umbilical cord mesenchymal/stromal stem cells are highly cytotoxic for myeloma cells both in vitro and in vivo.Stem cell research & therapy · 2017Article
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
Neuroendocrine tumors (NETs) metastasize to the skeleton in approximately 20% of patients. We have previously shown that the epithelial-mesenchymal transition (EMT) regulates the NET osteotropism and that CXCR4 overexpression predicts bone spreading. Here, we unravel the molecular mechanisms linking the activation of the CXCL12/CXCR4 axis to the bone colonization of NETs using cell lines representative of pancreatic (BON1, CM, QGP1), intestinal (CNDT 2.5), and bronchial origin (H727). By combining flow cytometry and ELISA, BON1, CM and QGP1 cells were defined as CXCR4high/CXCL12low, while H727 and CNDT 2.5 were CXCR4low/CXCL12high. CXCL12 was inert on cell proliferation, but significantly increased the in vitro osteotropism of CXCR4high/CXCL12low cells, as assessed by transwell assays with or without Matrigel membranes. In these cells, CXCL12 induced in vitro a marked EMT-like transcriptional shift with acquirement of a mesenchymal shape. The nuclei of CXCR4high/CXCL12low NET cells were typically enriched in non-phosphorylated CXCR4, particularly upon agonist stimulation. Silencing of CXCR4 via siRNA prevented the CXCL12-induced EMT in CXCR4high/CXCL12low NET cell lines resulting in the abrogation of both migration and transcriptional mesenchymal patterns. Our data suggest that CXCL12 conveys EMT-promoting signals in NET cells through CXCR4, which in turn regulates transcriptional, morphologic and functional modifications resulting in enhanced in vitro osteotropism of NET cells. Unique functions of CXCR4 may be segregated in relation to its subcellular localization and may acquire potential relevance in future in vivo studies.
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Registered trials
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