肝脏微环境细胞在肿瘤肝定植转移过程的作用及意义

The Role and Significance of Hepatic Environmental Cells in Tumor Metastatic Colonization to Liver

肿瘤转移是引起肿瘤患者死亡的主要原因,是临床上面临的重要挑战。肿瘤转移是个多步骤的复杂过程,肿瘤细胞历经离开原发部位,内渗进入血管,随血液远行,从血管外渗到远处器官,最终在靶器官定植(colonization)而生长成为转移性癌灶。肿瘤转移具有一定的靶器官亲嗜倾向,肝脏是肿瘤的常见转移部位,对肝脏有亲嗜倾向的肿瘤包括眼葡萄膜黑色素瘤、结直肠癌、胰腺癌等。肝脏解剖结构造成的血流动力学特点(例如压力小、血流慢)常常使得肿瘤细胞在肝脏易于瘀滞而利于定植,但肿瘤是否能在肝脏成功定植主要取决于肿瘤细胞与肝脏微环境(特别是肝固有细胞成分)的相互作用。肝脏微环境的固有细胞主要包括肝细胞、肝血窦内皮细胞(liver sinusoidal endothelial cells,LSECs)、肝星状细胞(hepatic stellate cells,HSCs)、枯否细胞(Kupffer cells,KCs)等。本文将讨论肝脏的固有细胞在肿瘤肝定植转移中的作用及意义。

Metastasis,a main cause of death in tumor patients,is a complicated process that involves multiple steps,presenting a major clinical challenge.Tumor cells break the physical boundaries of a primary tumor,intravasate into the lumina of blood vessels,travel around through blood circulation,extravasate into distant organs,colonize the host organs,and eventually develop into the foci of metastatic cancer.The metastasis of tumor cells exhibits organtropism,i.e.,tumor cells preferentially spread to specific organs.Liver is a common site for metastasis.The pattern of metastasis in uveal melanoma,colorectal carcinoma,and pancreatic ductal adenocarcinoma shows organ-tropism for liver.The anatomical structure of liver determines its hemodynamic characteristics,e.g.,low pressure and slow blood flow,which tend to facilitate the stasis and colonization of tumor cells in the liver.Besides the hemodynamic features,the metastatic colonization of liver depends largely on the interaction between tumor cells and the hepatic microenvironment(especially liver-resident cellular components).Resident cells of the hepatic microenvironment include hepatocytes,liver sinusoidal endothelial cells(LSECs),hepatic stellate cells(HSCs),Kupffer cells(KCs),etc.Herein,we discussed the role and significance of liver-resident cells in the metastatic colonization of tumor in the liver.