Zou Linghui, Xian Peng, Pu Qing, Song Yangjie, Ni Shuting, Chen Lei, Hu Kaili
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Acta Pharm Sin B. 2025 Apr;15(4):1841-1868. doi: 10.1016/j.apsb.2025.02.040. Epub 2025 Mar 8.
Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.
肿瘤转移是大多数癌症患者高死亡率的主要原因，大量研究表明，肿瘤微环境（TME）中多种成分的恶性相互作用共同促进了肿瘤转移。癌症相关成纤维细胞（CAFs）是各种肿瘤（如乳腺癌、胰腺癌和前列腺癌）TME中的主要基质细胞和相互作用中心。最近，CAF诱导的促肿瘤转移TME受到广泛关注，被认为是肿瘤治疗的有效靶点之一。随着深入研究，人们发现CAFs通过多种机制促进肿瘤转移，如诱导肿瘤细胞上皮-间质转化、重塑细胞外基质、保护循环肿瘤细胞以及促进前转移微环境的形成。为了增强抗肿瘤转移效果，将纳米药物递送系统与CAF调节相结合设计的治疗策略无疑是一个理想选择，过去几十年的研究证明了这一点。在此，我们介绍CAFs的生理特性，详细阐述CAFs促进肿瘤转移的可能机制，根据其抗转移功能对基于CAFs的纳米药物递送策略进行分类，并讨论当前面临的挑战、可能的解决方案以及未来的发展方向，以便为利用基于CAFs的纳米药物递送策略促进肿瘤转移治疗提供理论依据和参考。
