Relationship Between The Serum Level Of UPA/uPAR And Biological Behaviors In The Breast Carcinoma

Background and ObjectiveUrokinase Plasminogen activator (uPA) is one of the serine proteases.It operates on the cell surface affected whith urokinase plasminogen activator receptor (uPAR) and its inhibitor PAI-1, PAI-2,PAI-3.including urokinase plasminogen activator uPA; urokinase plasminogen activator receptor uPAR and its inhibitor PAI-1, PAI-2.They play an important role in the process of tumor invasion and metastasis with activating proteolytic enzymes. These proteolytic enzymes can degradate the extracellular matrix and the basement membrane.Tumor invasion and metastasis is a multifactorial course which requires the participation of proteolytic enzymes and their inhibitors. And the members of the umkinase plasminnogen actirator system are involved in these processes. uPA is secreted in the form of its first non-activity of single-chain zymogen, pro-uPA.It binds uPAR on cell surface, and pro-uPA by plasmin become the active form of uPA. The actived uPA could activate numbers of growth factors and promote epithelial membrane protein to degradate the matrix metalloproteinase (MMP), which takes part in the invasion and metastasis of the tumor. Besides,uPAR can regulate the capability of the tumor cells'adhesion and migration with PAI-1 and integrase.The former studies have shown that, the breast cancer patients with higher uPA and uPAR expression than normal peple,and the ones of mammary cancers with higher uPA and uPAR expression have a lower overall survival than the lower ones.The higher expression of uPA and uPAR is a character of the malignancy.With the farther studies going,we found the ability of the tumor cells'migration and invation is closely related to the foundation of the proteolytic enzymes.uPAR play an important role on that. And then node transfor and the tumor size are closely related with the lever of uPA and uPAR.Through the detection uPA/uPAR of lymph node-negative in breast cancers we found that uPA system is an independent prognostic factor, prognosis similar to the role and status of axillary lymph nodes. There also have researches poined out that uPA levels and estrogen receptor-related.These the levels of uPA,uPAR are lower are mor likely Estrogen receptor negative.In addition, There also have some reported shown that uPA or uPAR may equally predictade the effects of endocrine therapy for breast cancer and other treatment. So far, studies on the uPA system, have pointed out that these molecules of this system play an important role in tumor growth, and these proteins may be the target of cancer treatment.But In view of the detection of plasma uPA and PAI-1 concentration of researches are rare, while studies of the correlation between markers of uPA/uPAR with breast cancer immunohistochemical are not completly clear. And the researches on the relationship of molecular subtypes and uPA/uPAR are rare.Object:To investigate the expression levels of uPA and uPAR in plasma of breast cancer,and the relationship between mutation with the clinicpathological features of breast cancer and molecular subtypes.Methods:Experimental methods:The ELISA method was empolyeed to study the concentrations of uPA and uPAR in plasma of 86 breast carcinoma samples. All patients had a complete pathological data. The study is given informed consent.Statistical analysis:The SPSS 13.0 statistical software for analysis, P<0.05 indicated that the difference has a statistically significant.Results1. The concentration of uPA in plasma was prositively related to the tumor size of the breast cancer (P<0.05), histological grade (P<0.01), clinical stage (P<0.01),and axillary lymph node metastasis (P<0.01), and negatively with the patient's age, pathological subtype (P> 0.05); The concentration of uPAR in plasma of breast cancer pstients were positive correlated with tumor size (P<0.01), histological type (P<0.01),clinical stage (P<0.05), axillary lymph node metastasis (P<0.01) and negatively with age, pathological subtype (P> 0.05); 2. The concentration of uPA and uPAR in breast cancer patients with ER-positive expression was higher than the ER-negative patients (P<0.05). The status of PR had no relationship with uPA and uPAR concentration in plasma of brease cancer (P>0.05),The levels plasma of uPA and uPAR in breast cancer patients with HER-2 positive were higher than HER-2 negative patients (P<0.05).3. In molecular subtypes of breast cancer, the plasma levels of uPA (p<0.01), uPAR (P<0.05) had otherness.4. The plasama levels of uPA in breast cancer patients had a positive correlation with that of uPAR (P<0.01, r=0.735).ConclusionBreast cancer patients with high uPA and uPAR expression in plasma are closely related with tumor invasion and metastasis,the same with the ER status, HER2 expression and molecular subtypes;Combined detection of uPA,uPAR and molecular subtypes may be helpfull to determine the progress and predict biological behavior.