Target Discovery, Bayer Schering Pharma AG, Aprather Weg 18, 42096 Wuppertal, Germany.
Semin Cell Dev Biol. 2010 Feb;21(1):40-6. doi: 10.1016/j.semcdb.2009.11.017. Epub 2009 Nov 26.
Tumor development is critically dependent on the formation of a supporting stroma consisting of neovasculature, inflammatory cells and activated fibroblasts. Activated fibroblasts present a heterogeneous cell population not only in regard to the expression of marker molecules but also to their origin and molecular signaling properties. The plasticity of this cell type is pointed out by the multiple transdifferentiation events that lead to the generation of activated fibroblasts which can arise from resting fibroblasts, epithelial and endothelial cells as well as from mesenchymal stem cells. Cellular in vitro and in vivo experiments have changed the perspective of fibroblasts from passive "bystanders" in the tumor microenvironment to that of important drivers of tumor progression. Here, we describe the multiple origins of fibroblast recruitment to the tumor tissue as well as the function of activated fibroblasts during tumor initiation, progression, metastasis and anti-VEGF resistance. The identification of markers present in activated fibroblasts as well as a better understanding how these cells influence other tumor compartments has led to the clinical development of anti-tumor therapies.
肿瘤的发展严重依赖于支持基质的形成，该基质由新生血管、炎性细胞和激活的成纤维细胞组成。激活的成纤维细胞不仅在标记分子的表达上，而且在其起源和分子信号特性上，都是一个异质的细胞群体。这种细胞类型的可塑性表现在多种转分化事件上，这些事件导致了激活的成纤维细胞的产生，这些细胞可以来源于静止的成纤维细胞、上皮细胞和内皮细胞以及间充质干细胞。细胞的体外和体内实验改变了成纤维细胞在肿瘤微环境中从被动“旁观者”到肿瘤进展的重要驱动者的观点。在这里，我们描述了招募成纤维细胞到肿瘤组织的多种来源，以及激活的成纤维细胞在肿瘤起始、进展、转移和抗 VEGF 耐药性过程中的功能。鉴定出存在于激活的成纤维细胞中的标记物，并更好地了解这些细胞如何影响其他肿瘤细胞群，已经导致了抗肿瘤治疗的临床发展。
