摘要
Hepatocellular carcinoma(HCC) is one of the most common and deadly cancers worldwide. In ninety percent of the cases it develops as a result of chronic liver damage and it is thus a typical inflammationrelated cancer characterized by the close relation between the tumor microenvironment and tumor cells. The stromal environment consists out of several cell types, including hepatic stellate cells, macrophages and endothelial cells. They are not just active bystanders in the pathogenesis of HCC, but play an important and active role in tumor initiation, progression and metastasis. Furthermore, the tumor itself influences these cells to create a background that is beneficial for sustaining tumor growth. One of the key players is the hepatic stellate cell, which is activated during liver damage and differentiates towards a myofibroblast-like cell. Activated stellate cells are responsible for the deposition of extracellular matrix, increase the production of angiogenic factors and stimulate the recruitment of macrophages. The increase of angiogenic factors(which are secreted by macrophages, tumor cells and activated stellate cells) will induce the formation of new blood vessels, thereby supplying the tumor with more oxygen and nutrients, thus supporting tumor growth and offering a passageway in the circulatory system. In addition, the secretion of chemokines by the tumor cells leads to the recruitment of tumor associated macrophages. These tumor associated macrophages are key actors of cancer-related inflammation, being the main type of inflammatory cells infiltrating the tumor environment and exerting a tumor promoting effect by secreting growth factors, stimulating angiogenesis and influ-encing the activation of stellate cells. This complex interplay between the several cell types involved in liver cancer emphasizes the need for targeting the tumor stroma in HCC patients.
Hepatocellular carcinoma （HCC） is one of the mostcommon and deadly cancers worldwide. In ninetypercent of the cases it develops as a result of chronicliver damage and it is thus a typical inflammationrelatedcancer characterized by the close relationbetween the tumor microenvironment and tumor cells.The stromal environment consists out of several celltypes, including hepatic stellate cells, macrophages andendothelial cells. They are not just active bystandersin the pathogenesis of HCC, but play an importantand active role in tumor initiation, progression andmetastasis. Furthermore, the tumor itself influencesthese cells to create a background that is beneficialfor sustaining tumor growth. One of the key players isthe hepatic stellate cell, which is activated during liverdamage and differentiates towards a myofibroblastlikecell. Activated stellate cells are responsible forthe deposition of extracellular matrix, increase theproduction of angiogenic factors and stimulate therecruitment of macrophages. The increase of angiogenicfactors （which are secreted by macrophages, tumor cellsand activated stellate cells） will induce the formation ofnew blood vessels, thereby supplying the tumor withmore oxygen and nutrients, thus supporting tumorgrowth and offering a passageway in the circulatorysystem. In addition, the secretion of chemokines by thetumor cells leads to the recruitment of tumor associatedmacrophages. These tumor associated macrophagesare key actors of cancer-related inflammation, being themain type of inflammatory cells infiltrating the tumorenvironment and exerting a tumor promoting effect bysecreting growth factors, stimulating angiogenesis andinflu-encing the activation of stellate cells. This complexinterplay between the several cell types involved in livercancer emphasizes the need for targeting the tumorstroma in HCC patients.
