肿瘤干细胞与肿瘤相关巨噬细胞的相互作用

Crosstalk Between Cancer Stem Cells and Tumor Associated Macrophages

肿瘤微环境(tumor microenvironment,TME)不仅促进了肿瘤的早期形成和远处转移,而且随着肿瘤的进展,其自身也不断地发生变化。作为TME的重要组成部分,肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)可通过分泌多种细胞因子激活IL-6/STAT3、TGF-β、Wnt/β-catenin等信号通路促进肿瘤干细胞(cancer stem cells,CSCs)的存活、自我更新和化疗耐药等。同时,CSCs也可通过分泌多种细胞因子和趋化因子等募集巨噬细胞,并将其诱导为TAMs重塑CSCs特定的生态位,维持CSCs表型并促进肿瘤进展。TAMs与CSCs的相互作用在促进肿瘤生长、转移及化疗耐药等方面发挥了重要作用。本文对TME中CSCs与TAMs相互作用的研究进行综述,并总结了以CSCs与TAMs相互作用为靶点在新型癌症治疗以及增强化疗效果等方面的重要潜力。

Tumor microenvironment(TME)not only promotes the early formation and distant metastasis of tumors but also changes constantly with the progress of tumors.Cancer stem cells(CSCs)are self-renewing cells that facilitate tumor initiation,promote metastasis,and enhance cancer therapy resistance.The crosstalk between CSCs with cancer cells and other non-CSCs occurs in cancers,which is possible under the control of signals from CSCs and TME,including CSCs niche.As an important immune cell in CSCs niche,tumor-associated macrophages(TAMs)are among the most influential cells for promoting CSCs survival,and self-renewal.TAMs can activate IL-6/STAT3,TGF-β,Wnt/β-catenin,and other signaling pathways by secreting a series of cytokines to promote survival,self-renewal,and resistance to chemotherapy of CSCs.At the same time,CSCs also play an important role in promoting the recruitment of macrophages and inducing their transformation into M2 TAMs to promote tumor progression.CSCs recruit macrophages into TME through various secretory factors such as POSTN,MIF,CCL2,M-CSF,I L-6,IL-1β,TNF-α,etc,and then polarize to the M2 phenotype under the action of PGE2,WISP,IL-10,GM-CSF,MIC-1,and other chemokines and cytokines,shaping immunosuppressive and tumor-promoting TME.Therefore,the interaction between TAMs and CSCs plays an important role in promoting tumor growth,metastasis,and chemoresistance.This paper reviews the research progress on the interaction between CSCs and TAMs in TME and the potential target in the interaction of CSCs and TAMs for novel cancer therapy.These emerging insights provide a roadmap for the development of novel anti-cancer therapeutic strategies that disrupt this dynamic circuit in specific tumor types.