Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment
Gallbladder cancer (GBC) is a highly aggressive malignancy with a propensity for lymph node metastasis (LNM), which significantly worsens prognosis. This review explores the molecular mechanisms underlying LNM in GBC, focusing on the roles of vascular endothelial growth factors (VEGFs), chemokines,...
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MDPI AG
2025-06-01
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| author | Qingyu Tang Yichen Guan Yubo Ma Qi Li Zhimin Geng |
| author_facet | Qingyu Tang Yichen Guan Yubo Ma Qi Li Zhimin Geng |
| author_sort | Qingyu Tang |
| collection | DOAJ |
| description | Gallbladder cancer (GBC) is a highly aggressive malignancy with a propensity for lymph node metastasis (LNM), which significantly worsens prognosis. This review explores the molecular mechanisms underlying LNM in GBC, focusing on the roles of vascular endothelial growth factors (VEGFs), chemokines, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), hypoxia-inducible factors (HIFs), and non-coding RNAs (ncRNAs) in shaping the tumor microenvironment (TME). Unique features of GBC, such as its bile-rich microenvironment and hypoxia-driven lymphangiogenesis, are highlighted. We discuss how these factors promote lymphangiogenesis, immune evasion, and extracellular matrix (ECM) remodeling, collectively facilitating LNM. Potential therapeutic targets, including VEGF-C/D pathways, matrix metalloproteinase (MMP) inhibitors, and immune-modulating therapies, are also reviewed. Future research integrating single-cell omics and patient-derived organoid models is essential for advancing precision medicine in GBC. |
| format | Article |
| id | doaj-art-286e5b89b40d4adbaf676cff17ddb2ab |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-286e5b89b40d4adbaf676cff17ddb2ab2025-08-20T03:27:26ZengMDPI AGBiomedicines2227-90592025-06-01136137210.3390/biomedicines13061372Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor MicroenvironmentQingyu Tang0Yichen Guan1Yubo Ma2Qi Li3Zhimin Geng4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaGallbladder cancer (GBC) is a highly aggressive malignancy with a propensity for lymph node metastasis (LNM), which significantly worsens prognosis. This review explores the molecular mechanisms underlying LNM in GBC, focusing on the roles of vascular endothelial growth factors (VEGFs), chemokines, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), hypoxia-inducible factors (HIFs), and non-coding RNAs (ncRNAs) in shaping the tumor microenvironment (TME). Unique features of GBC, such as its bile-rich microenvironment and hypoxia-driven lymphangiogenesis, are highlighted. We discuss how these factors promote lymphangiogenesis, immune evasion, and extracellular matrix (ECM) remodeling, collectively facilitating LNM. Potential therapeutic targets, including VEGF-C/D pathways, matrix metalloproteinase (MMP) inhibitors, and immune-modulating therapies, are also reviewed. Future research integrating single-cell omics and patient-derived organoid models is essential for advancing precision medicine in GBC.https://www.mdpi.com/2227-9059/13/6/1372gallbladder cancerlymph node metastasistumor microenvironmentnon-coding RNAsvascular endothelial growth factor |
| spellingShingle | Qingyu Tang Yichen Guan Yubo Ma Qi Li Zhimin Geng Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment Biomedicines gallbladder cancer lymph node metastasis tumor microenvironment non-coding RNAs vascular endothelial growth factor |
| title | Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment |
| title_full | Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment |
| title_fullStr | Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment |
| title_full_unstemmed | Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment |
| title_short | Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment |
| title_sort | molecular mechanisms of lymph node metastasis in gallbladder cancer insights into the tumor microenvironment |
| topic | gallbladder cancer lymph node metastasis tumor microenvironment non-coding RNAs vascular endothelial growth factor |
| url | https://www.mdpi.com/2227-9059/13/6/1372 |
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