Institute of Physiological Chemistry, University of Ulm, 89081 Ulm, Germany.
Int J Mol Sci. 2020 Jul 31;21(15):5486. doi: 10.3390/ijms21155486.
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal cancer. The poor prognosis calls for a more detailed understanding of disease biology in order to pave the way for the development of effective therapies. Typically, the pancreatic tumor is composed of a minority of malignant cells within an excessive tumor microenvironment (TME) consisting of extracellular matrix (ECM), fibroblasts, immune cells, and endothelial cells. Research conducted in recent years has particularly focused on cancer-associated fibroblasts (CAFs) which represent the most prominent cellular component of the desmoplastic stroma. Here, we review the complex crosstalk between CAFs, tumor cells, and other components of the TME, and illustrate how these interactions drive disease progression. We also discuss the emerging field of CAF heterogeneity, their tumor-supportive versus tumor-suppressive capacity, and the consequences for designing stroma-targeted therapies in the future.
胰腺导管腺癌（PDAC）仍然是一种致命的癌症。由于预后不良，需要更深入地了解疾病生物学，为开发有效的治疗方法铺平道路。通常，胰腺肿瘤由少数恶性细胞组成，这些细胞位于由细胞外基质（ECM）、成纤维细胞、免疫细胞和内皮细胞组成的过度肿瘤微环境（TME）中。近年来的研究特别关注癌症相关成纤维细胞（CAFs），它是纤维状基质中最突出的细胞成分。在这里，我们综述了 CAFs、肿瘤细胞和 TME 其他成分之间的复杂相互作用，并说明了这些相互作用如何推动疾病进展。我们还讨论了 CAF 异质性这一新兴领域，以及它们的肿瘤支持与肿瘤抑制能力，以及对未来靶向基质治疗设计的影响。
