Expression of Urokinase-type Plasminogen Activator (uPA), uPA Receptor, and Plasminogen Activator Inhibitor-1 in Oral Squamous Cell Carcinoma / Oral Science International

We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (<i>p</i> < 0.001, <i>p</i> < 0.001, and <i>p</i> < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (<i>p</i> < 0.05 and <i>p</i> < 0.001, respectively), while both were associated with tumor size (<i>p</i> < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (<i>p</i> < 0.01) and PAI-1 (<i>p</i> < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.

Adenoid Cystic Carcinoma : Participation of Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR) in Tumor Invasion / Oral Science International

Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α₂ integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α₂ integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.

Adenoid Cystic Carcinoma: Participation of Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR) in Tumor Invasion / Oral Science International

Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α₂ integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α₂ integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.

Expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in hepatocellular carcinoma and its clinical and pathological significance / 中国微创外科杂志

0.05). Positive stains were located in cytoplasm of cancer and stromal cells, especially in invasive margin of cancer. Slight positive stains were observed in non-cancer tissues. But in the control samples, there wasn't specific stain. In ELISA, the uPA antigen levels in cancer and non- cancer tissues were (4.23?0.57)ng/mg protein and (1.26?0.14)ng/mg protein; the uPAR antigen levels in caner and non-cancer tissues were(4.25?0.21)ng/mg protein and (3.15?0.23)ng/mg protein respectively. Significant difference existed in both uPA and uPAR antigen levels in these two kinds of tissue ( t=18.963,P=0.000;t=13 693,P=0 000 ). Furthermore, these antigen levels in progressive and aggressive tumors significantly higher than those in non-progressive and non-aggressive tumors ( P

The effect of hypoxia on uPA activity in human tongue carcinoma cell line Tca8113 / 实用口腔医学杂志

Objective:To observe the activity of urokinase-type plasminogen activator (uPA) in human tongue squamous cell carcinoma cell line Tca8113 under hypoxia in vitro. Methods:According to the different time of hypoxia, the test was divided into four groups as following: (1) 0 h; (2) 6 h;(3)12 h;(4)24 h. The expression of uPA was examined using immunochemistry. The expression of uPA mRNA was examined using in situ hybridization (ISH). The results of ISH staining of uPA mRNA were analysed using Spot and IPP image analysis system.Results:The uPA expression was found in cytoplasm and cytomembrane of Tca8113 cells.uPA mRNA expression was found in cytoplasm of the cells.The staining intensity of uPA mRNA in the groups of (1),(2),(3) and (4) was 0.175 251?(0.013) 863,0.263 191?(0.000 680),0.406 745?0.014 016 and 0.478 919?0.018 998 respectively(P

Expression of Urokinase-type Plasminogen Activator(uRA), Plasminogen Activator Inhibitor-1(PAI-1) and nm23 protein, as Prognostic Factors in Epithelial Ovarian Cancer / 대한부인종양콜포스코피학회잡지

The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.

Expression of Urokinase-type Plasminogen Activator(uRA), Plasminogen Activator Inhibitor-1(PAI-1) and nm23 protein, as Prognostic Factors in Epithelial Ovarian Cancer / 대한부인종양콜포스코피학회잡지

The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.