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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Main Authors: Qingyu Tang, Yichen Guan, Yubo Ma, Qi Li, Zhimin Geng
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/6/1372
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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.
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institution Kabale University
issn 2227-9059
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publishDate 2025-06-01
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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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