Gumberger Peter, Bjornsson Bergthor, Sandström Per, Bojmar Linda, Zambirinis Constantinos P
Department of Surgery, Linköping University, 58183 Linköping, Sweden.
Department of Biomedical and Clinical Sciences, Linköping University, 58183 Linköping, Sweden.
Cancers (Basel). 2022 Jun 20;14(12):3028. doi: 10.3390/cancers14123028.
Cancer-related mortality is primarily a consequence of metastatic dissemination and associated complications. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and tends to metastasize early, especially in the liver. Emerging evidence suggests that organs that develop metastases exhibit microscopic changes that favor metastatic growth, collectively known as "pre-metastatic niches". By definition, a pre-metastatic niche is chronologically established before overt metastatic outgrowth, and its generation involves the release of tumor-derived secreted factors that modulate cells intrinsic to the recipient organ, as well as recruitment of additional cells from tertiary sites, such as bone marrow-all orchestrated by the primary tumor. The pre-metastatic niche is characterized by tumor-promoting inflammation with tumor-supportive and immune-suppressive features, remodeling of the extracellular matrix, angiogenic modulation and metabolic alterations that support growth of disseminated tumor cells. In this paper, we review the current state of knowledge of the hepatic pre-metastatic niche in PDAC and attempt to create a framework to guide future diagnostic and therapeutic studies.
癌症相关死亡率主要是转移扩散及相关并发症的结果。胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，且往往早期就发生转移，尤其是在肝脏。新出现的证据表明，发生转移的器官会出现有利于转移生长的微观变化，统称为“前转移微环境”。根据定义，前转移微环境是在明显的转移灶形成之前按时间顺序建立的，其形成涉及肿瘤衍生分泌因子的释放，这些因子可调节受体器官固有的细胞，以及从三级部位（如骨髓）募集额外的细胞，这一切均由原发肿瘤精心安排。前转移微环境的特征是具有促进肿瘤生长的炎症，伴有支持肿瘤生长和免疫抑制的特性、细胞外基质重塑、血管生成调节以及支持播散性肿瘤细胞生长的代谢改变。在本文中，我们综述了目前关于PDAC肝前转移微环境的知识现状，并试图创建一个框架以指导未来的诊断和治疗研究。
