Sunami Yoshiaki, Häußler Johanna, Kleeff Jörg
Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle, Germany.
Cancers (Basel). 2020 Dec 15;12(12):3770. doi: 10.3390/cancers12123770.
Pancreatic cancer is projected to become the second deadliest cancer by 2030 in the United States, and the overall five-year survival rate stands still at around 9%. The stroma compartment can make up more than 90% of the pancreatic tumor mass, contributing to the hypoxic tumor microenvironment. The dense stroma with extracellular matrix proteins can be a physical and metabolic barrier reducing therapeutic efficacy. Cancer-associated fibroblasts are a source of extracellular matrix proteins. Therefore, targeting these cells, or extracellular matrix proteins, have been considered as therapeutic strategies. However, several studies show that deletion of cancer-associated fibroblasts may have tumor-promoting effects. Cancer-associated fibroblasts are derived from a variety of different cell types, such as pancreatic stellate cells and mesenchymal stem cells, and constitute a diverse cell population consisting of several functionally heterogeneous subtypes. Several subtypes of cancer-associated fibroblasts exhibit a tumor-restraining function. This review article summarizes recent findings regarding origin and functional heterogeneity of tumor-promoting as well as tumor-restraining cancer-associated fibroblasts. A better understanding of cancer-associated fibroblast heterogeneity could provide more specific and personalized therapies for pancreatic cancer patients in the future.
预计到2030年，胰腺癌将成为美国第二大致命癌症，总体五年生存率仍停留在9%左右。基质部分可占胰腺肿瘤质量的90%以上，导致肿瘤微环境缺氧。含有细胞外基质蛋白的致密基质可能成为降低治疗效果的物理和代谢屏障。癌症相关成纤维细胞是细胞外基质蛋白的来源。因此，靶向这些细胞或细胞外基质蛋白被视为治疗策略。然而，多项研究表明，删除癌症相关成纤维细胞可能具有促肿瘤作用。癌症相关成纤维细胞来源于多种不同的细胞类型，如胰腺星状细胞和间充质干细胞，构成了一个由几种功能异质亚型组成的多样化细胞群体。癌症相关成纤维细胞的几种亚型具有肿瘤抑制功能。这篇综述文章总结了关于促肿瘤和抑肿瘤癌症相关成纤维细胞的起源和功能异质性的最新发现。更好地了解癌症相关成纤维细胞的异质性可能为未来的胰腺癌患者提供更具体、个性化的治疗方法。
