Activated Hepatic Stellate Cells In The Pathogenesis Of Hepatocellular Carcinoma: Evidence For A Role Of MEF2 And Its Association With Alteration Of Histone Acetylation

BackgroundsHepatocellular carcinoma is the fifth most common cancer worldwide (＞1,000,000 new cases/year)and the third most common cause of cancer death (＞500,000 deaths/year).In China,it represents the second cause of cancer-related death.In the last several decades there have been important gains in our understanding of the pathogenesis of HCC.The most accepted hypothesis describes a step-by-step process in which external stimuli induce genetic/epigenetic alterations in mature hepatocytes resulting in the progression of normal cells through preneoplastic states into invasive cancers.However,none of the findings has turned into a breakthrough in the prevention ang treatment for HCC.Much of the research concerning the origins of HCC has focused on the genetic/epigenetic mutations within malignant transformed hepatocytes themselves.In fact,it is increasingly apparent the stromal cells profoundly influence many steps of tumor progression.Genetic and cell-biology studies indicate that tumor growth is not just determined by malignant cancer cells themselves,but also by tumor stroma.The stroma,composed of mesenchymal cells that are involved in angiogenesis and the response to injury,such as activated fibroblasts,myofibroblasts,inflammatory cells, endothelial cells,is associated with cancer cells at all stages of cancer progression.