肿瘤相关成纤维细胞促进肿瘤侵袭转移的作用机制

肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)是肿瘤微环境中最主要的成分之一,在肿瘤的发生发展中发挥着必不可少的作用。骨髓和脂肪的局部组织固有成纤维细胞及间充质干细胞是CAFs来源的主要前体细胞。大量研究表明,CAFs并不作为单独细胞在肿瘤周围存在,而是和肿瘤细胞相互作用,促进肿瘤的生长与存活并维持其恶性倾向。肿瘤细胞可以影响CAFs前体的招募,并诱导正常成纤维细胞活化为CAFs;同时,CAFs可以分泌多种细胞因子、生长因子和细胞外基质蛋白质,促进肿瘤细胞的增殖、耐药及侵袭转移,从而影响肿瘤的预后。CAFs还参与血管淋巴管的生成、细胞外基质重塑、免疫抑制以及肿瘤细胞上皮间质转化等有利于肿瘤发生发展的外源性途径,为肿瘤细胞提供了一个良好的微环境。大量研究显示,研发靶向CAFs的药物可以中断其与肿瘤细胞之间的联系,从而抑制肿瘤的生长和转移。因此,深入了解CAFs促肿瘤的作用机制将有利于肿瘤治疗新靶点的发现。本文将对CAFs促进肿瘤侵袭转移的作用机制加以综述。

Mechanism of Cancer-associated Fibroblasts Promoting Tumor Metastasis and Invasion

Cancer-associated fibroblasts (CAFs) are one of the most important components of the tumor microenvironment, which play an indispensable role in promoting occurrence and progression of tumor. Tissue-resident fibroblasts and mesenchymal stem cells coming from bone marrow and adipose tissue are the main progenitor cells of CAFs. Numerous studies showed that CAFs don’t exist as isolated cells around the tumor, they interact closely with tumor cells and promote tumor growth and survival and maintain malignancy. Tumor cells can influence CAFs precursor recruitment and induce the activation of normal fibroblasts. CAFs can promote the proliferation, chemoresistance, invasion and metastasis of tumor cells by secreting various cytokines, growth factors and extracellular matrix proteins, resulting in poor prognosis. CAFs participate in the exogenous pathways that are favorable for the occurrence of tumors, such as angiogenesis, extracellular matrix remodeling, immunosuppression and epithelial-mesenchymal transition, which create a suitable microenvironment for tumor cells. Many studies have reported that developing CAFs-targeting drugs may disrupt their association with tumor cells, thereby inhibit tumor growth and metastasis. Therefore, understanding the mechanism of CAFs in promoting tumorigenesis will provide useful information for the discovery of novel targets for tumor therapy. This review summarizes the role of CAFs in tumor metastasis.