The Studies Of Relationship Between Invasiveness Pituitary Adenoma And Expression, Regulation Of UPA System

Pituitary adenoma is a kind of common encephalic tumor,originate from anterior lobe of pituitary gland accounts for 10% in all encephalic tumors. Most pituitary adenomas are benign tumors, but some of them show malignant biological properties, such as highly proliferation and invasiveness. So it is difficult to resect completely and recurrent frequently. According to the biological properties of pituitary adenomas, the tumors can be divided into invasive and non-invasive adenoma. In 1964, Jefferson first put forward the concept of invasive adenoma, which breakthrough the surrounding membranes and adjoining structure with biological properties between benign and malignant. The date reported morbidity of invasive adenomas 6%-85%.The progression and invasion of tumor requires various factors and multiple procedures to participate. The invasive capacity is related to its ability to induce proteolytic to degradate Extracelluar matrix(ECM) and Basement membrane(BM). Degradation of ECM and angiogenesis is a premise for the invasion and metastasis of tumor. Urokinase type plasminogen activator system uPAs (uPA,uPAR,PAI-1) is closely related to the metastasis, invasion of tumor cells and the formation of angiogenesis. uPA and uPAR activates plasminogen, changing it to plasmin, degradating ECM , membrane fibrin, proteoglycan. PAI-1, an effective inhibitor to uPA, plays an important role in maintaining the equilibrium of protein degradation . So far , almost no reports about the expression of serine proteases in pituitary adenomas have been seen. The basic Fibroblastic Growth Factor, as an angiogenesis factor, plays a vital controlling in growth of tissues . bFGF , combined its receptor , contributes to the expression of uPA/uPAR ; uPA and uPAR combined may contribute to secretion of growth factors . uPA and uPAR combined , is in proportion with bFGF : with large quantities of uPA , degradation of ECM, contributing to the invasiveness of tumor cells. aminepolyglucosides is another major component of ECM , whose component is heparan sulfate proteoglycans , heparanase. HPA is a newly-cloned enzyme , degradated and connected at the core of HS. HPA can induce HS to react the following biological reactions :①degradating HSPGs,destroying ECM and BM ;②releasing bFGF combined on HS , helping growth and metastasis of tumor ;③releasing uPA on HS , dissolving the network structure of MMPs.In order to investigate the relationship between the expression and angiogenesis and invasiveness of pituitary adenoma , forty-one surgically removed pituitary adenomas were divided into invasive group of 21 cases , non-invasive group of 20 cases and 5 cases of normal pituitary gland .Through immunohistochemistry the expression was tested of uPA, PAI-1 , bFGF in each group , taking accounts of MVD .By means of Western blotting ,the expression of uPA and HPA was tested . By means of RT-PCR, the transcription of nucleic acid of uPA, HPA mRNA was tested.This research has found out : the positive expression rates of uPA in the invasive group is obviously higher than those of the non-invasive group . There are significant differences in mean value of MVD between invasive pituitary adenomas group and non-invasive adenomas group with 30.67±7.47 for the invasive group and 20.30±8.17 for the non-invasive group. In the invasive group , uPA is in proportion to PAI-1 (p<0.01). Besides, by means of RT-PCR ,transcription of uPA, HPAmRNA nucleic acid was analyzed and tested; by means of Western blotting, the expression of uPA, HPA was tested . That has proved the relationship between uPA and invasive adenoma . In the invasive group, HPA is in proportion to uPA.The following conclusions have been drawn : the expression of uPA system, bFGF , HPA is closely related to invasive adenoma . uPA and bFGF may play a coordinating and adapting role in the invasion of adenoma . HPA may contribute to the expression of uPA . uPA system , bFGF , HPA play an important role in contributing to the invasion of adenoma and the growth of tumorigenesis . uPA system , bFGF , HPA all may act as biological marks of the invasive adenoma . Further research into the growth and development of uPA in protelysis, may well provide theories and practices upon which to base earlier diagnosis , prognosis of invasive adenoma, and provide therapeutic targets for curing tumor.