ArticleGenes2020
Lymphatic Metastasis of NSCLC Involves Chemotaxis Effects of Lymphatic Endothelial Cells through the CCR7-CCL21 Axis Modulated by TNF-α.
Article in Genes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation.NPJ Regenerative medicine · 2026Review
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Transforming Cancer Therapy: Unlocking the Potential of Targeting Vascular and Stromal Cells in the Tumor Microenvironment.Cancer research · 2025Review
- Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.Cancer medicine · 2024Article
- Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.World journal of hepatology · 2024Review
- Advances in lymphatic metastasis of non-small cell lung cancer.Cell communication and signaling : CCS · 2024Review
- Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.Science translational medicine · 2023Article
- Circ_0060967 facilitates proliferation, migration, and invasion of non-small-cell lung cancer cells by sponging miR-660-3p/UBN2.Molecular and cellular biochemistry · 2023Article
- Hepatic lymphatic vascular system in health and disease.Journal of hepatology · 2022Review
- Paclitaxel treatment enhances lymphatic metastasis of B16F10 melanoma cells via CCL21/CCR7 axis.International journal of biological sciences · 2022Article
- The prospect of immunotherapy combined with chemotherapy in patients with advanced non-small cell lung cancer: a narrative review.Annals of translational medicine · 2021Review
- Identification of a competing endogenous RNA axis "SVIL-AS1/miR-103a/ICE1" associated with chemoresistance in lung adenocarcinoma by comprehensive bioinformatics analysis.Cancer medicine · 2021Article
- High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification.Genome medicine · 2021Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis and recurrence are the main causes of lung adenocarcinoma patients' death. Lymphatic metastasis is the main way of non-small cell lung cancer (NSCLC) metastasis. C-C chemokine receptor type 7 (CCR7) overexpression has been demonstrated to mediate occurrence and progression of NSCLC. Moreover, Chemokine ligand 21 (CCL21) was used to activate CCR7. The CCR7-CCL21 axis is one of the most common "chemokine-receptor" modes of action in the development and metastasis of multiple tumors. However, the role of the CCR7-CCL21 axis in lymphatic metastasis of NSCLC is poorly understood. The study was conducted to investigate the molecular mechanism underlying CCR7-CCL21 axis-mediated lymphatic metastasis of NSCLC A549 cells. Tumor necrosis factor α (TNF-α) could regulate the tumor microenvironment balance by promoting chemokine secretion. Our study demonstrated that TNF-α promoted CCL21 production in human lymphatic endothelial cells (HLEC). Results further showed that TNF-α significantly activated the NF-κB pathway in HLEC. NF-κB pathway inhibition with ammonium pyrrolidinedithiocarbamate (PDTC) caused a significant decrease in CCL21 secretion, suggesting that TNF-α-induced CCL21 secretion in HLEC was through NF-κB pathway. Co-culture of A549 cells and TNF-α-treated HLEC confirmed that the metastasis of A549 cells was enhanced, meanwhile, apoptosis-related proteins were hardly affected. The data proved that a co-culture system prevented cell apoptosis while inducing the lymphatic metastasis of A549 cells. However, the situation was reversed after neutralizing CCL21 expression, suggesting that TNF-α-induced CCL21 secretion in HLEC is involved in A549 cells metastasis. Collectively, our finding demonstrated that NF-κB pathway-controlled CCL21 secretion of HLEC contributing to the lymphatic metastasis of A549 cells via the CCR7-CCL21 axis, validating the CCR7-CCL21 axis as a potential target to inhibit metastasis of NSCLC.
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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.