肿瘤相关成纤维细胞促进肿瘤化疗耐药的作用机制

The Mechanism Underlying the Promoting Effect of Cancer-associated Fibroblasts on Chemoresistance

肿瘤的发生发展不仅取决于肿瘤细胞自身的特性,还与肿瘤细胞所处的微环境密切相关。大量研究显示,肿瘤微环境(tumor microenvironment,TME)在肿瘤的发展和耐药等过程中发挥着至关重要的作用。肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)是TME中重要的基质细胞组分,具有多种功能,例如重塑细胞外基质、调节血管生成,以及与相邻的肿瘤细胞相互作用,释放多种旁分泌信号(细胞因子、生长因子和外泌体等)参与调控肿瘤细胞的增殖、侵袭转移等过程。在TME中,CAFs表现出来源和表型的异质性及其促进/抑制肿瘤进展的双向作用。最新研究表明,CAFs还可以介导肿瘤细胞的治疗抵抗,因此,CAFs本身和其下游效应分子及信号通路可能成为肿瘤治疗的潜在靶点。本综述重点关注CAFs在不同肿瘤中赋予治疗抗性方面的作用及其潜在机制,最后讨论了靶向CAFs在克服肿瘤治疗抗性方面的新兴策略和前景。然而,针对CAFs的靶向治疗策略的探索尚处在早期阶段,需要进一步的深入研究。

The carcinogenesis and progression of cancer not only depend on the feature of tumor cell themselves,but also rely on the tumor microenvironment(TME).Numerous studies have shown that TME plays a crucial role in tumor progression and drug resistance.Cancer-associated fibroblasts(CAFs)are important stromal cells in TME containing multiple functions,such as remodeling the extracellular matrix,regulating angiogenesis,interacting with adjacent tumor cells,and releasing a variety of molecules(such as cytokines,growth factors and exosomes)to regulate cell proliferation,invasion and metastasis.CAFs exhibit heterogeneity of origin and phenotype,and play dual roles in tumor progression.Recent studies have shown that CAFs are also involved in chemoresistance,suggesting that CAFs themselves and their downstream molecules and signal pathways could be the potential therapeutic target for cancer treatment.In this review,we summarized the role of CAFs in chemoresistance and underlying mechanism,and discussed the potential of targeting CAFs in overcoming drug resistance.However,the exploration of strategy for targeting CAFs is still at an early stage and requires further in-depth research.