Clinical Significance Of HMGB1Expression Between The Normal And Hepatocellular Carcinoma Cells

Background The high-mobility group box1protein (HMGB1) is present in almost all metazoans and plants. It was first identified as one of a group of chromatin-associated protein with high acidic and basic amino acid content HMGB1is a highly conserved nuclear protein, acting as a chromatin-binding factor that bends DNA and promotes access to transcriptional protein assemblies on specific DNA targets.In addition to its nuclear role, HMGB1also functions as an extracellular signaling molecule during inflammation, cell differentiation, cell migration, and tumor metastasis.HMGB1is passively released from necrotic cells and is actively secreted by inflammatory cells, binding with high affinity to several receptors including the receptor for advanced glycation end products (RAGE), Toll-like receptors and as a negative signaling molecule, mediating the response to infection and injury, thereby promoting inflammation.HMGB1has been implicated in disease states, includingsepsis,ischemia-reperfusion, arthritis,neurodegeneration, aging, and cancer.Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide, with a very poor prognosis. Hepatocellular carcinoma causes662,000deaths worldwide per year about half of them in China. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or liver cirrhosis.Increased expression of HMGB1has been reported for several different tumour types, including gastrointestinal stromal tumours, breast carcinoma, colorectal cancer, prostate cancer and pancreatic cancer. Many studies suggest that over expression of HMGBl has been strongly correlated with tumour genesis and tumour metastasis. HMGB1plays a major role in angiogenesis,apoptosis and autophagy dependent on the cell type and antecedent stress. And along with other intracellular factors released from tumor cells induced by chemotherapy or radiotherapy, is an important component of the disordered tumor microenvironment. Expression of RAGE is closely associated with the invasive and metastatic activity of cancer.Inhibition of the RAGE-HMGB1interaction suppresses activation of p44/p42, p38and SAP/JNK MAP kinases. These molecular effector mechanisms are linked to tumor proliferation, invasion and expression of matrix metalloproteinases (MMPs). We all know that matrix metalloproteinases are essential to the invasive and metastatic activity of cancer. So HMGB1take some part in the invasive and metastatic activity of cancer.Cheng’s study show that the serum HMGB1levels in patients with hepatocellular carcinoma was significantly higher than those with chronic hepatitis,liver cirrhosis. HMGB1also correlated with Edmondson grades I, Ⅱ, Ⅲ, Ⅳ and TNM stages Ⅰ, Ⅱ, Ⅲ, Ⅳ. HMGB1may play an important role not only in development of HCC but in metastasis and poor outcome. It also could be a useful and specific marker for evaluating the tumour differentiation grade,tumour stage and predicting prognosis in patients with HCC.This relatively new concept helps us to understand the pathogenesis of HCC and might provide insights that targeting HMGB1production or release might have substantial potential applications for HCC treatment.Background and objective To investigate the expression of high mobility group protein box1(HMGB1) in human hepatocellular carcinoma cells.Methods PCR and Western blot were performed to study HMGB1gene expression at the mRNA and protein levels in hepatocellular carcinoma cells (LM3and HEPG2). A normal cell line (LO2) was used as an control.Results The expression levels of the HMGB1gene (mRNA and protein) were much higher in hepatocellular carcinoma cells LM3and HEPG2than in LO2(P <0.05). Moreover, HMGB1expression was also higher in the highly metastatic hepatocellular carcinoma LM3cells than in the less metastatic hepatocellular carcinoma HEPG2cells (P<0.05)Conclusion The high expression of HMGB1in hepatocellular carcinoma cells suggestss that it may play an important role in the growth and metastasis of hepatocellular carcinoma.