ArticleCells2021
Tumor Lymphatic Interactions Induce CXCR2-CXCL5 Axis and Alter Cellular Metabolism and Lymphangiogenic Pathways to Promote Cholangiocarcinoma.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Tumor-associated lymphatic vessel density is a postoperative prognostic biomarker of hepatobiliary cancers: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- CXCL5: A coachman to drive cancer progression.Frontiers in oncology · 2022Pooled it
- The CXCL5/CXCR2 Axis Attenuates Ferroptosis in Intrahepatic Cholangiocarcinoma Through the Positive Feedback Loop Between PTGS2 Transcriptional Activation and Neutrophil Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Exosomal Oleic Acid Promotes Lymphangiogenesis and Nodal Metastasis in Cervical Cancer via the AKT/mTOR Pathway.Journal of extracellular vesicles · 2026Article
- MDA-9/Syntenin small molecule inhibitor IVMT-Rx-4 blocks prostate cancer bone metastasis.Pharmacological research · 2026Article
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment.Biomedicines · 2025Review
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- Chemokines and their receptors in the esophageal carcinoma tumor microenvironment: key factors for metastasis and progression.Frontiers in oncology · 2025Review
- The C-X-C Motif Chemokine Ligand 5, Which Exerts an Antioxidant Role by Inducing HO-1 Expression, Is C-X-C Motif Chemokine Receptor 2-Dependent in Human Prostate Stroma and Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry.Communications biology · 2024Article
- Tumor lymphangiogenesis index reveals the immune landscape and immunotherapy response in lung adenocarcinoma.Frontiers in immunology · 2024Article
- Targeting Glycolytic Reprogramming in Cholangiocarcinoma: A Novel Approach for Metabolic Therapy.Journal of inflammation research · 2024Review
- Review
- Role of the tumor microenvironment in the lymphatic metastasis of cervical cancer (Review).Experimental and therapeutic medicine · 2023Review
- Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes.International journal of molecular sciences · 2023Article
- Article
- Cellular Senescence as a Brake or Accelerator for Oncogenic Transformation and Role in Lymphatic Metastasis.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignancy characterized by early lymphangiogenesis in the tumor microenvironment (TME) and lymph node (LN) metastasis which correlate with adverse patient outcome. However, the specific roles of lymphatic endothelial cells (LECs) that promote LN metastasis remains unexplored. Here we aimed to identify the dynamic molecular crosstalk between LECs and CCA cells that activate tumor-promoting pathways and enhances lymphangiogenic mechanisms. Our studies show that inflamed LECs produced high levels of chemokine CXCL5 that signals through its receptor CXCR2 on CCA cells. The CXCR2-CXCL5 signaling axis in turn activates EMT (epithelial-mesenchymal transition) inducing MMP (matrix metalloproteinase) genes such as GLI, PTCHD, and MMP2 in CCA cells that promote CCA migration and invasion. Further, rate of mitochondrial respiration and glycolysis of CCA cells was significantly upregulated by inflamed LECs and CXCL5 activation, indicating metabolic reprogramming. CXCL5 also induced lactate production, glucose uptake, and mitoROS. CXCL5 also induced LEC tube formation and increased metabolic gene expression in LECs. In vivo studies using CCA orthotopic models confirmed several of these mechanisms. Our data points to a key finding that LECs upregulate critical tumor-promoting pathways in CCA via CXCR2-CXCL5 axis, which further augments CCA metastasis.
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What OpenQuestion holds
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.