Molecular Mechanisms of Lymph Node Metastasis in Gallbladder Cancer: Insights into the Tumor Microenvironment

TL;DR

This paper reviews how gallbladder cancer spreads to lymph nodes by altering the tumor environment through various molecular factors.

Contribution

The paper provides a comprehensive overview of the molecular pathways involved in lymph node metastasis specific to gallbladder cancer.

Findings

VEGFs, chemokines, and CAFs contribute to lymph node metastasis by altering the tumor microenvironment.

Hypoxia and non-coding RNAs play key roles in promoting lymphangiogenesis and immune evasion.

VEGF-C/D pathways and MMP inhibitors are potential therapeutic targets for treating gallbladder cancer.

Abstract

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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