title: The activation of protease-activated receptor 1 mediates proliferation             and invasion of nasopharyngeal carcinoma cells.
abstract: Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein, which is involved in physiological and malignant invasion processes. It is activated by serine proteases such as thrombin through a unique form or by specific synthetic peptides. In this study, we determined the expression of PAR-1 in five nasopharyngeal carcinoma (NPC) cell lines with different characteristics of invasiveness and metastasis, and found that the levels of PAR-1 expression were higher in invasive or metastatic cell lines than those in low invasive or metastatic ones. Of the five NPC cell lines, CNE1-LMP1 cells had the highest expression levels of PAR-1, which was mainly distributed at the membrane and in the cytoplasm of tumor cells. Further study showed that the thrombin receptor synthetic activating peptide SFLLRN could stimulate the growth of CNE1-LMP1 cells in a dose-dependent manner. However, thrombin itself had a dual effect on the proliferation of NPC cells. Concentrations of thrombin in the range of 0.1-0.5 U/ml promoted cell growth, but concentrations higher than 0.5 U/ml impaired cell growth. Moreover, thrombin and SFLLRN also enhanced the invasive capabilities of CNE1-LMP1 cells in vitro, and this was partly due to enhancing the activities of MMP-2 and MMP-9. Our findings suggest that PAR-1 may contribute to the growth and invasive potential of NPC cells.
authors.affiliation: Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Qingyao
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jianchao
authors.initials: J
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Ren
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms; D010446:Peptide Fragments / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D010446:Peptide Fragments; D044463:Receptor, PAR-1; C082835:thrombin receptor peptide (42-47); D013917:Thrombin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9