Department of Oncology, University of Wisconsin, Madison, WI 53705, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Drug Discov Today. 2018 Mar;23(3):548-564. doi: 10.1016/j.drudis.2018.01.020. Epub 2018 Jan 9.
Hepatocellular carcinoma (HCC) disseminates systemically, but metastases occur in distant organs only in minority of patients, whereas HCC routinely metastasizes to liver and its vessels. HCC cells disseminate via hepatic veins, but portal veins are affected by metastasis more frequently than are hepatic veins, and correlates with poor prognosis. In this review, I suggest that privileged HCC portal metastasis occurs because of high levels of pancreatic family hormones and growth factors (PHGFs) in the portal blood. The analysis suggests that the appearance of the portal system carrying PHGFs in the evolution of invertebrate chordate (Amphioxus) led to the evolution of the liver in vertebrate; given that the portal pattern of HCC metastasis and selection of more-aggressive clones are PHGF dependent, PHGFs and their ligands constitute therapeutic targets.
肝细胞癌 (HCC) 会全身扩散，但只有少数患者的转移会发生在远处器官，而 HCC 通常会转移到肝脏及其血管。HCC 细胞通过肝静脉扩散，但门静脉比肝静脉更容易受到转移的影响，并且与预后不良相关。在这篇综述中，我提出门静脉优先转移 HCC 是由于门静脉血液中高水平的胰腺家族激素和生长因子 (PHGFs) 所致。分析表明，携带 PHGFs 的门静脉系统在无脊椎脊索动物（文昌鱼）的进化中出现，导致了脊椎动物肝脏的进化；鉴于 HCC 转移的门静脉模式和更具侵袭性克隆的选择依赖于 PHGF，因此 PHGFs 及其配体构成了治疗靶点。
