利用细胞邻近标记研究早期肿瘤微环境  

Dissecting Early-Stage Tumor Microenvironment with Niche-Labeling

作　　者：黄涵英 赵闯 谭志鸿 田麟 HUANG Hanying;ZHAO Chuang;TAN Zhihong;TIAN Lin(State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]华南恶性肿瘤防治全国重点实验室,广东省恶性肿瘤临床医学研究中心,中山大学肿瘤防治中心,广州510060

出　　处：《中国细胞生物学学报》2025年第3期534-540,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金面上项目(批准号:82173278);广州市科技计划(批准号:202201011364)资助的课题。

摘　　要：肿瘤是一个恶性生态系统,它不仅由癌变的肿瘤细胞组成,还包括成纤维细胞、内皮细胞、血管周皮细胞、组织驻留细胞和各种免疫细胞等基质细胞。这些基质细胞构成肿瘤微环境(tumor microenvironment,TME),在肿瘤的发生、进展、转移和治疗耐药中发挥着关键作用,而不仅仅是作为旁观者。大多数关于TME的临床前研究和临床研究都集中在可见的肿瘤,对活检的恶性肿瘤组织进行免疫组化染色或单细胞多组学分析。然而,晚期TME变得异常复杂,使得许多治疗策略无效。因此,研究癌细胞与肿瘤基质之间的相互作用是必要的,最好是从肿瘤起始或小肿瘤集群开始。荧光标记或生化标记在肿瘤进展过程中接近癌细胞或与癌细胞相互作用的基质细胞,为研究侵袭性肿瘤生态系统的演变提供了有希望的方法,并具有在TME形成中识别新的治疗靶点的潜力。在此,该文概述了不同研究早期肿瘤微环境的细胞邻近标记技术,并讨论了如何将这些系统应用于识别新的肿瘤–基质相互作用,提供了将这些生态位标记系统与原发肿瘤模型相结合的见解。Tumor represents a malignant ecosystem,composed not only of transformed cancer cells but also of stromal cells,including fibroblasts,endothelial cells,pericytes,tissue-resident cells,and various immune cells.These stromal cells,which constitute the TME(tumor microenvironment),play critical roles in tumor initiation,progression,metastasis,and therapeutic resistance,rather than merely acting as bystanders.Most preclinical and clinical studies on the TME focus on overt tumors,where malignant biopsies are dissected for immunostaining or single-cell multi-omics profiling.However,the TME at late stages becomes exceedingly complex,rendering many therapeutic strategies ineffective.Therefore,it is imperative to investigate the interactions between cancer cells and tumor stroma at much earlier stages,ideally from tumor initiation or cancer cell micro-clusters.Fluorescently labeling or biochemically tagging stromal cells that are in proximity to or interact with cancer cells during tumor progression presents promising approaches for studying the evolution of aggressive tumor ecosystems and holds the potential to identify novel therapeutic targets for emerging TME.This review provides an overview of various niche-labeling techniques for studying tumor microenvironment,discusses how these systems have been applied to identify novel tumor-stroma interactions,and offers insights into combining these tools with autochthonous tumor models.

关 键 词：肿瘤微环境 邻近标记 脂溶性穿膜红色荧光蛋白 转肽酶A 合成Notch受体 

分 类 号：R73[医药卫生—肿瘤]