成纤维细胞在肝癌发生发展中的作用

The role of liver fibroblasts in the occurrence and development of hepatocellular carcinoma

肝脏发生纤维化及进一步产生的肝硬化是肝癌发生发展的重要因素。成纤维细胞可以使细胞外基质沉积,而细胞外基质沉积也是肝脏纤维化的标志性改变。成纤维细胞有多种来源,主要是由于肝损伤的性质不同。目前认为成纤维细胞主要来源于肝星状细胞(Hepatic stellate cells,HSCs),亦称为Ito细胞。在肝细胞癌(Hepatocellular carcinoma,HCC)的发生发展过程中肝成纤维细胞可以转化为肿瘤相关成纤维细胞(Cancer-associated fibroblasts,CAFs)。活化的肝星状细胞(Activated HSCs,AHSCs)/CAFs在HCC的发生发展中的作用已经被证实。CAFs是HCC中的肿瘤微环境(The tumor microenvironment,TME)中一组具有不同细胞来源和表型的活化成纤维细胞,与肿瘤的发生发展密切相关。CAFs可能通过分泌多种生长因子和细胞因子,促进细胞外基质重塑、增强肝癌细胞的干性、促进肿瘤耐药、促进肝癌的血管生成和血管生成拟态(Vasculogenic mimicry,Vm)来影响肿瘤细胞的增殖、凋亡、迁移、侵袭、血管生成、免疫逃逸和耐药性。由于存在上述特性,CAFs可以作为肿瘤治疗中的理想靶点。在这篇综述中,我们将对HCC中CAFs的最新认识、其细胞起源以及生物学功能进行阐释。

Liver fibrosis and further cirrhosis are important factors in the occurrence and development of liver cancer.Fibroblasts can deposit extracellular matrix,and extracellular matrix deposition is also a hallmark of liver fibrosis.Liver fibrosis and further cirrhosis are important factors in the occurrence and development of liver cancer.There are many sources of fibroblasts,and the different sources are mainly due to the different nature of liver damage.It is currently believed that fibroblasts are mainly derived from hepatic stellate cells(Hepatic stellate cells,HSCs),also known as Ito cells.Liver fibroblasts can transform into cancer-associated fibroblasts(CAFs)during the occurrence and development of hepatocellular carcinoma(HCC).The role of activated hepatic stellate cells(activated HSCs,AHSCs)/tumor-associated fibroblasts(CAFs)in the occurrence and development of HCC has been confirmed.CAFs are a group of activated fibroblasts with different cell sources and phenotypes in the tumor microenvironment(TME)of HCC,and are closely related to the occurrence and development of tumors.CAFs may secrete a variety of growth factors and cytokines,promote extracellular matrix remodeling,enhance the stemness of liver cancer cells,promote tumor resistance,promote liver cancer angiogenesis and vasculogenic mimicry(Vm)to affect tumors cell proliferation,apoptosis,migration,invasion,angiogenesis,immune escape and drug resistance.Because of the above characteristics,CAFs can be used as ideal targets in tumor treatment.In this review,we will explain the latest understanding of HCC CAFs,their cell origin and biological functions.