The Relationship Between Polymorphonuclear Leukocyte Elastase Secreted From Renal Cell Carcinoma And The Tumor Prognosis

Renal cell carcinoma (RCC), which accounts for about 3% of all adult malignancy tumors, is the most lethal of the urologic cancers. Although tumor size, tumor grades and nuclear atypia of RCC have been reported as prognostic factors, the biological behavior of this tumor is still unpredictable. Polymorphonuclear leukocyte elastase (PMNE) is a powerful serine protease, since it degrads most protein components of the extracellular matrix, it is suggested to play a crucial role in the processes of some tumor cell invasion and metastasis, including non-small cell lung carcinoma and primary breast cancer. Because there is no published information on the relation between the level of PMNE and prognosis in patients of RCC, we, in this study, explored if PMNE level was involved in the prognosis of RCC patients. Using molecular, immunological and pathological methods, we measured levels of PMNE incytoplasmic extracts of 59 renal cell carcinomas and observed microvascular invasion of RCC cells and sequenced PMNE promoter gene of RCC, which showed single nucleic acid mutant whose promoter activity was also compared with wild type PMNE promoter through inserting both promoters into pGL3-Basic to construct luciferase expression vector. Results:1. The PMNE was over expressed in RCC cell and the level of PMNE in the tissue extract of T3a and T3b RCC was much more higher than those of T1 and T2, So we conclude that the level of PMNE expression in RCC cell is closely related to the TNM staging2. High level PMNE expression was detected in the specimen of RCC with microvascular invasion, which indicated that the PMNE over expression in RCC might be related to the tumor invasion into microvascular.3. One important finding of this study was that there were 1 cases of RCC whose PMNE promoter gene sequence had permutation mutant from C to A occurred in the -879th and -716th base of region3 6.4. Luciferase expressed in K562 cells transfected with mutant PMNE promoter luciferase expression vector was considerablely higher than those transfected with wild type PMNE promoter luciferase expression vector, which suggests that PMNE promoter occurred in RCC enhanced this enzyme activity.CONCLUSION:PMNE is over expressed in RCC and the level of its expression is closely related with the stage and the invasion abilities of the tumor. PMNE promoter gene permutation mutant in the region 3 6 may be the cause of higher activity of PMNE enzyme, which promoted the invasion of RCC cell within the matrix. Our data indicated that PMNE may play an important role in the development of RCC.