The Expression Of Functional Formylpeptide Receptor On Human Hepatoma Cells

Hepatocellular carcinoma (HCC) is one of the most common cancers of the world which has high disease rate and mortality. In our country HCC is the second reason of death for malignant tumors. It was proved that invasion and metastasis was the main reason for the bad endings of HCC patients. So the predication and treatment of invasion and metastasis become one of the key points for the researches of HCC.Previous studies on chemokines and their receptors mainly focused on their functions mediating inflammatory processes. In recent years, these receptors have been found to play an extensive and complicated role in carcinogenesis. Many chemokines have been detected in malignant tumors, and multiple chemokine receptors have also been demonstrated to be expressed by tumor cells. Some of these receptors suppress tumor growth through chemotaxis, activation of immune cells and suppression of angiogenesis, while others promote tumor growth and metastasis through enhancing tumor cell mobility, attracting tumor cell invasion, promoting vascular proliferation and degradation of extracellular matrix. It was demonstrated that some chemoattractant receptors that are expressed on normal cells and related to certain physiological or pathophysiological courses are also expressed in cancer cells and take roles in the progression of the cancer, which is a complicated process involves multiple faces and stages of interplays between cancer cells and host tissues, among which the increased capacity of cell proliferation and motility, overexpressed protease and proangiogenic factors, and their dysregulation during the cancer -host interplay are the most important part of the research, and the related receptors may be potential therapeutic targets.The formylpeptide receptors (FPR) are members of a class of G protein-coupled receptors involved in chemotaxis, containing FPR, FPRL1, and FPRL2. FPR was first defined biochemically in 1976. Upon ligand binding, FPR undergoes a conformation change enabling interactions with G family proteins. Agonist-induced signaling also results in phosphorylation of protein kinases (PI3K,MAPK and NF-κB) and regulation of cellular activations and migration. FPR was reported that it expressed on many normal tissues and cells, such as some epithelial cells, liver hepatocytes and Kupffer cells, smooth muscle and endothelial cells, brain and spinal cord, and so on. FPR was expressed by malignant glioma and related to the degree of malignancy and microvessel density within glioma tissue. The significance of functional FPR in cancer therapy needs further studies.For a better understanding of the possible role and significance and mechanism of FPR in hepatocellular carcinoma growth and invasion activity, we investigated the expression of FPR in human hepatocellular carcinoma cells HepG2 and Hep3B, and examined their contributions to invasion activity. Moreover, we also explored whether the FPR expressed in hepatocellular carcinoma tissues. The main results and conclusions are as follows:1. By RT-PCR and FACS analysis, we found that both two human hepatocellular carcinoma cell lines HepG2 and Hep3B expressed the FPR.2. FMLF has a chemotactic effect on both HepG2 and Hep3B cells. By western blot analysis, when FPR activated by fMLF, ERK were phosphorylated, MAPK/ERK signaling pathway is activated.3. We investigated IL-8 production following activation of hepatocellular carcinoma cells by FPR using ELISA.4. By immunohistochemistry assay, we found that FPR was expressed in hepatocellular carcinoma tissues.