Liver Tropism in Cancer: The Hepatic Metastatic Niche
Liver Tropism in Cancer: The Hepatic Metastatic Niche
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DOI：
10.1101/cshperspect.a037259
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发表时间：
2020-03-01
影响因子：
5.4
通讯作者：
Schmid, Michael C.
中科院分区：
文献类型：
--
作者：
Mielgo, Ainhoa;Schmid, Michael C.
肝脏是人体最大的器官，容易发生癌症转移。虽然转移模式可以根据癌症类型而不同，但对于大多数流行的恶性肿瘤，肝脏是癌细胞最常转移的器官。肝脏在几个方面是独特的：血管结构具有高度渗透性，具有无与伦比的双重血液连通性，肝脏组织微环境为播散性肿瘤细胞的播种提供了天然土壤。虽然肝脏的70%由实质肝细胞组成，但剩余的30%由非实质细胞组成，包括枯否细胞、肝窦内皮细胞和肝星状细胞。最近的发现表明，实质细胞和非实质细胞都可以调节肝转移级联反应的每一步，包括最初的播种和定植以及进行休眠与生长的决定。因此，更好地理解协调形成好客的肝转移小生境的分子机制，并确定支持这一过程的驱动因素，对于开发更好的治疗方法来阻止或至少减少肝转移至关重要。该观点的重点是散布的癌细胞和独特的肝脏转移生态位之间的双向相互作用。
The liver is the largest organ in the human body and is prone for cancer metastasis. Although the metastatic pattern can differ depending on the cancer type, the liver is the organ to which cancer cells most frequently metastasize for the majority of prevalent malignancies. The liver is unique in several aspects: the vascular structure is highly permeable and has unparalleled dual blood connectivity, and the hepatic tissue microenvironment presents a natural soil for the seeding of disseminated tumor cells. Although 70% of the liver is composed of the parenchymal hepatocytes, the remaining 30% is composed of nonparenchymal cells including Kupffer cells, liver sinusoidal endothelial cells, and hepatic stellate cells. Recent discoveries show that both the parenchymal and the nonparenchymal cells can modulate each step of the hepatic metastatic cascade, including the initial seeding and colonization as well as the decision to undergo dormancy versus outgrowth. Thus, a better understanding of the molecular mechanisms orchestrating the formation of a hospitable hepatic metastatic niche and the identification of the drivers supporting this process is critical for the development of better therapies to stop or at least decrease liver metastasis. The focus of this perspective is on the bidirectional interactions between the disseminated cancer cells and the unique hepatic metastatic niche.