Wang Zimu, Liu Jiaxin, Huang Hairong, Ye Mingxiang, Li Xinying, Wu Ranpu, Liu Hongbing, Song Yong
Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, #305, East Zhongshan Road, 210002, Nanjing, Jiangsu, China.
Department of Cardiothoracic Surgery, Jinling Hospital, 210002, Nanjing, China.
Biomark Res. 2021 Jun 10;9(1):47. doi: 10.1186/s40364-021-00305-9.
Metastasis suggests a poor prognosis for cancer patients, and treatment strategies for metastatic cancer are still very limited. Numerous studies have shown that cancer-associated fibroblasts (CAFs), a large component of the tumor microenvironment, contribute to tumor metastasis. Stromal fibroblasts at metastatic sites are different from CAFs within primary tumors and can be termed metastasis-associated fibroblasts (MAFs), and they also make great contributions to the establishment of metastatic lesions and the therapeutic resistance of metastatic tumors. MAFs are capable of remodeling the extracellular matrix of metastatic tumors, modulating immune cells in the tumor microenvironment, promoting angiogenesis and enhancing malignant tumor phenotypes. Thus, MAFs can help establish premetastatic niches and mediate resistance to therapeutic strategies, including immunotherapy and antiangiogenic therapy. The results of preclinical studies suggest that targeting MAFs can alleviate the progression of metastatic cancer and mitigate therapeutic resistance, indicating that MAFs are a promising target for metastatic cancer. Here, we comprehensively summarize the existing evidence on MAFs and discuss their origins, generation, functions and related therapeutic strategies in an effort to provide a better understanding of MAFs and offer treatment perspectives for metastatic cancer.
转移提示癌症患者预后不良，而转移性癌症的治疗策略仍然非常有限。大量研究表明，癌症相关成纤维细胞（CAFs）作为肿瘤微环境的重要组成部分，促进肿瘤转移。转移部位的基质成纤维细胞不同于原发性肿瘤内的CAFs，可称为转移相关成纤维细胞（MAFs），它们对转移灶的形成和转移性肿瘤的治疗抵抗也有很大贡献。MAFs能够重塑转移性肿瘤的细胞外基质，调节肿瘤微环境中的免疫细胞，促进血管生成并增强恶性肿瘤表型。因此，MAFs有助于建立前转移微环境并介导对包括免疫疗法和抗血管生成疗法在内的治疗策略的抵抗。临床前研究结果表明，靶向MAFs可缓解转移性癌症的进展并减轻治疗抵抗，这表明MAFs是转移性癌症的一个有前景的靶点。在此，我们全面总结了关于MAFs的现有证据，并讨论它们的起源、产生、功能及相关治疗策略，以期更好地理解MAFs并为转移性癌症提供治疗思路。
