The expression and the functional roles of tissue factor and protease-activated receptor-2 on SW 620 cells

Tissue factor (TF) is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Protease-activated receptors (PARs) are widely expressed on various cells including tumor cells and associated with many pathological mechanisms. In the present study, the expression of TF and PAR1, PAR2 on human colon cancer cells (SW620 and SW480) was investigated and their functional roles on the behavior of tumor cells were evaluated. It was demonstrated that SW620 and SW480 cells expressed TF at antigen, activity and mRNA levels. However, the highly metastatic cell line SW620 showed slightly higher TF expression than the low metastatic cell line SW480. The PAR2 antigen was strongly expressed on the membrane of SW620 cells, but not on SW480 cells. The PAR1 antigen was not observed in SW620 or SW480 cells, while PAR1 and PAR2 mRNA was detected in SW620 and SW480 cells. The migratory potential of SW620 was stronger than that of SW480 seen in Boyden chambers. PAR2 agonist (SLIGKV-NH2) and factor VIIa significantly stimulated SW620 cell proliferation, migratory activity, and interleukin 8 (IL-8) secretion compared to control. The stimulating effects of factor VIIa could be inhibited by anti-TF and anti-PAR2 but not anti-PAR1 antibodies. In summary, this study demonstrates that TF and PAR2 are strongly expressed on highly metastatic colonic tumor cells and are closely associated with the proliferation and migration of the cells. TF may elucidate its roles in colonic cancer invasion and metastasis via PAR2 pathway.

[1]  U. Pendurthi,et al.  Modulation of Tissue Factor–Factor VIIa Signaling by Lipid Rafts and Caveolae , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[2]  J. Trejo,et al.  Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer , 2007, Journal of Cell Science.

[3]  J. Trejo,et al.  Cryptic messages: Is noncoagulant tissue factor reserved for cell signaling? , 2006, Proceedings of the National Academy of Sciences.

[4]  H. Versteeg,et al.  Disulfide isomerization switches tissue factor from coagulation to cell signaling , 2006, Proceedings of the National Academy of Sciences.

[5]  S. Arii,et al.  Tissue factor is a useful prognostic factor of recurrence in hepatocellular carcinoma in 5-year survivors. , 2005, Hepato-gastroenterology.

[6]  T. Aikou,et al.  Interleukin 8 in Human Hepatocellular Carcinoma Correlates With Cancer Cell Invasion of Vessels But Not With Tumor Angiogenesis , 2005, Annals of Surgical Oncology.

[7]  M. Hollenberg,et al.  Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. , 2005, Human pathology.

[8]  S. Hirohashi,et al.  Prognostic Significance of Tissue Factor in Pancreatic Ductal Adenocarcinoma , 2005, Clinical Cancer Research.

[9]  S. Shirasawa,et al.  Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. , 2005, Blood.

[10]  R. Lefkowitz,et al.  Constitutive Protease-activated Receptor-2-mediated Migration of MDA MB-231 Breast Cancer Cells Requires Both β-Arrestin-1 and -2* , 2004, Journal of Biological Chemistry.

[11]  L. Brass,et al.  Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis. , 2004, Molecular cancer research : MCR.

[12]  N. Mackman.  Role of tissue factor in hemostasis, thrombosis, and vascular development. , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[13]  W. Ruf,et al.  Protease-activated Receptor 2-dependent Phosphorylation of the Tissue Factor Cytoplasmic Domain* , 2004, Journal of Biological Chemistry.

[14]  U. Pendurthi,et al.  Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. , 2004, Blood.

[15]  Xiaofeng Jiang,et al.  Formation of tissue factor–factor VIIa–factor Xa complex promotes cellular signaling and migration of human breast cancer cells , 2004, Journal of thrombosis and haemostasis : JTH.

[16]  S. Fan,et al.  Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  Steven Patierno,et al.  Tissue factor, thrombin, and cancer. , 2003, Chest.

[18]  T. Peretz,et al.  Human protease-activated receptor 1 expression in malignant epithelia: a role in invasiveness. , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[19]  T. Hembrough,et al.  Tissue factor/factor VIIa inhibitors block angiogenesis and tumor growth through a nonhemostatic mechanism. , 2003, Cancer research.

[20]  K. Muramoto,et al.  Neutrophil Serine Proteinases Activate Human Nonepithelial Cells to Produce Inflammatory Cytokines Through Protease-Activated Receptor 21 , 2003, The Journal of Immunology.

[21]  M. Laburthe,et al.  Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induces cell proliferation and motility in human colon cancer cells. , 2003, The American journal of pathology.

[22]  S. Coughlin,et al.  Genetic Evidence That Protease-activated Receptors Mediate Factor Xa Signaling in Endothelial Cells* , 2002, The Journal of Biological Chemistry.

[23]  K. Xie,et al.  Interleukin-8 and human cancer biology. , 2001, Cytokine & growth factor reviews.

[24]  N. Bunnett,et al.  Protease-activated receptors: how proteases signal to cells. , 2001, Current opinion in pharmacology.

[25]  M. Bromberg,et al.  Role of Protease-activated Receptor 1 in Tumor Metastasis Promoted by Tissue Factor , 2001, Thrombosis and Haemostasis.

[26]  Jennifer L. Harris,et al.  Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates* , 2000, The Journal of Biological Chemistry.

[27]  N. Lemoine,et al.  Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma , 1999, The British journal of surgery.

[28]  K. Nabeshima,et al.  Analysis of tissue factor and tissue factor pathway inhibitor expression in human colorectal carcinoma cell lines and metastatic sublines to the liver , 1997, International journal of cancer.

[29]  W. Konigsberg,et al.  Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  T S Edgington,et al.  Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[31]  N. Callander,et al.  Immunohistochemical identification of tissue factor in solid tumors , 1992, Cancer.

[32]  I. Fidler,et al.  Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. , 1990, Cancer research.

[33]  J. Trejo,et al.  Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells. , 2006, Cancer research.

[34]  D. Richel,et al.  Tissue Factor and Cancer Metastasis: The Role of Intracellular and Extracellular Signaling Pathways , 2004, Molecular medicine.

[35]  G. D. Hunter,et al.  Proteinase-activated receptors. , 2001, Pharmacological reviews.