Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma

Xue YU; Tianhao SHEN; Cheng ZHOU; Yu LIU; Tinghui JIANG; Wei LI; Yongqiang ZHU; Yan LIU

doi:10.19401/j.cnki.1007-3639.2025.10.008

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Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma

Review | 更新时间：2025-12-31

- Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma
- China Oncology Vol. 35, Issue 10, Pages: 952-958(2025)
- 作者机构：
  
  1. 上海中医药大学附属普陀医院肿瘤介入科，上海 200062
  2. 上海中医药大学附属普陀医院肿瘤介入研究所，上海 200062
  3. 上海中医药大学附属普陀医院肝胆外科，上海 200062
- 作者简介：
  
  LIU Yan
- 基金信息：
  
  Shanghai Municipal Health Commission Youth Talent Program(2022YQ037);The Science and Technology Innovation Project Plan of the Health and Wellness System of Putuo District, Shanghai(ptkwws202210)
- DOI：10.19401/j.cnki.1007-3639.2025.10.008
  CLC： R735.8
- Received：21 August 2024，
  
  Revised：2025-06-26，
  
  Published：30 October 2025
- 稿件说明：
移动端阅览
Xue YU, Tianhao SHEN, Cheng ZHOU, et al. Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma[J]. China Oncology, 2025, 35(10): 952-958.
DOI：

Xue YU, Tianhao SHEN, Cheng ZHOU, et al. Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma[J]. China Oncology, 2025, 35(10): 952-958. DOI： 10.19401/j.cnki.1007-3639.2025.10.008.

摘要

胆管癌作为一种侵袭性强且预后较差的恶性肿瘤，其转移机制复杂，亟待深入研究。循环肿瘤细胞（circulating tumor cell，CTC）作为从原发部位脱落进入血液循环的关键肿瘤细胞类型，对肿瘤的转移具有重要的研究意义。近年来，研究发现，CTC的侵袭性伪足在肿瘤细胞迁移和侵袭中发挥了重要作用。其中，在信号转导通路方面的研究进展表现在：Rho家族GTP酶（RhoA、Rac1、Cdc42）分工协同调控伪足收缩力、肌动蛋白分支聚合及导向，磷脂酰肌醇3-激酶（phosphoinositide3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）信号转导通路通过激活AKT促进肌动蛋白组装并与Rho家族交叉对话；在分子机制上的研究进展包括：长链非编码RNA通过吸附miRNA等方式调控伪足相关基因表达，基质金属蛋白酶（matrix metalloproteinase，MMP）降解细胞外基质（extracellular matrix，ECM）形成侵袭正反馈；在微环境方面的研究进展包括：癌相关成纤维细胞（cancer-associated fibroblast，CAF）和巨噬细胞分泌的转化生长因子-β（transforming growth factor-beta，TGF-β）、表皮生长因子（epidermal growth factor，EGF）、白细胞介素-6（interleukin-6，IL-6）等细胞因子激活伪足形成信号转导通路，ECM硬度与纤维排列通过机械力传导影响伪足伸展。本文通过对CTC的生物学特性、胆管癌细胞侵袭性伪足的形成机制、胆管癌细胞的转移特征及其临床意义、CTC在胆管癌转移过程中的作用进行综合分析，总结现有研究成果并探讨潜在的治疗靶点，为胆管癌防治研究工作者提供参考。

Abstract

Cholangiocarcinoma

as a malignant tumor with strong invasiveness and poor prognosis

has a complex metastasis mechanism

and urgently needs in-depth research. Circulating tumor cells (CTC)

as the key cell type for tumor cells to shed from the primary site and enter the bloodstream

have significant research significance. In recent years

studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells. Among them

in terms of signal transduction pathways

the Rho family GTPases (RhoA

Rac1

Cdc42) work in coordination to regulate the contractility of the pseudofoot

the branching polymerization and orientation of actin

and the phosphoinositide3-kinase/protein kinase B (PI3K/AKT) pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT. At the molecular mechanism level

long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means. Matrix metalloproteinase (MMP) degrades the extracellular matrix (ECM) to form an invasion positive feedback. In terms of the microenvironment

cancer-associated fibroblast (CAF) and the cytokines such as transforming growth factor-β (TGF-β) secreted by macrophages

epidermal growth factor (EGF)

and interleukin-6 (IL-6) activate pseudopodia to form signal transduction pathways. ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction. This article conducted a comprehensive analysis of the biological characteristics of CTC

the formation mechanism of invasive pseudopodia in cholangiocarcinoma

the metastatic features of cholangiocarcinoma cells and their clinical significance

as well as the role of CTC in the metastatic process of cholangiocarcinoma

in order to summarize the existing research results

explore potential therapeutic targets and future research directions

and provide new ideas for the clinical treatment of cholangiocarcinoma.

关键词

Keywords

references

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