The Study Of The Relationship Between Hepatocyte Growth Factor And Metastasis Of Lung Cancer

Objective:①To investigate the effects of HGF on motility, invasiveness andgrowth of human NSCLC cell lines and study the expression of HGFreceptor C-met on them. To observe the effects of HGF and VEGF on theangiogenesis of HUAECs.②To study the serium concentration of HGF in the NSCLC patientsand the expresssion of HGF in lung cancer tissues. To evaluate theprobability of HGF in the early diagnosis and prognosis of lungcancer.Methods:Using Western blot and immunocytochemistry studies to measure theexpression of the C-met(the receptor of HGF/SF) and using the Northernblot to measure the existance of C-met mRNA. Cell motility assay,invasion assay and spreading assay were used to detect the abilityof HGF on the motility, invasivness and spreading of 5 lung cancercell lines.Endothelial cell proliferation and capillary sprouts formationtests were used to evaluate the effects of HGF and VEGF on angiogenesisof human umbilical artery endothelial cells. ELISA was used to measurethe content of HGF/SF and VEGF in the media. The patients who underwent surgical treatment were sampled beforeoperation and 1,3,7,14 days post-operation. The healthy controland benign thoracic disease groups also had thire blood samplemeasured. The concentration of HGF in serium was determined by ELISA.The expression of HGF in the tumor and normal lung tissues wasmeasured by immunohistochemistry method. Results: ①The expression of C-met protein in the lung cancer cell lineswas found by the Western blot and the immunocytochemistry studies.TheC-met mRNA in the lung cancer cell lines was also detected by theNorthern blot. ②The motility,spreading ability and invasiveness of the lungcancer cell lines had been significantly increased by HGF. ③HGF and VEGF had obvious effects on endothelial cellproliferation and capillary sprouts formation. The VEGF was found inHGF media. ④HGF serium concentration in lung cancer patients (470.7±378.4pg/ml) was significantly higher than that of normal healthycontrol (223.3±93pg/ml) and lung benign disease patients(189.0±170.1pg/ml) (P<0.05). 46 patients had underwent 2 yearsfollowing-up, of which, 16 patients died and their serium HGFcontents(741.8 ±665.1pg/ml) was significantly higher than 30survivors'(420.9±177.1pg/ml)(P<0.05) in the 14th day post-operation.The survival rate of 21 patients whose serium HGF level was lowerthan 400pg/ml were significantly higher than that of ≥400pg/mlpatients'(P<0.05). HGF serium concentraion of lung cancer patientsat day 3 post-operation was significantly higher than that of lungbenign disease patients (P<0.05). Serium HGF content of survivorsduring the follow-up period gradually decreased at day 7 and day 14after operation, but serum HGF content of 16 dead patients in 2 yearsat day 14 after operation was still higher (741.8±665.1pg/ml) thanthat before operation's (P<0.05). ⑤HGF expression rate in the 49 resected samples was 63.3%(31/49).The expression of HGF had statistical associations with the clinicalstages and lymph node metastasis. HGF-positive rate in stage IIIpatients is 85.7%, higher than that in stage I and IIpatients(46.4%)(P<0.005). HGF-positive rates in N1 and N2 patients was91.7% and 90.9% respectively, whereas HGF-positive rates in N0patients is (46.2%)( P<0.005); 2 years survival in HGF-positive groupand HGF-negative group are 54.8% and 88.9% respectively (p<0.05)。 Conclusion: According to the researches above, we conclude thatHGF has almostly participated in the whole course of the tumormetastasis. These foundings have partly revealed the molecularmechanism of the tumor metastasis and set a labarotory basis forfurther research on the relations between HGF and the tumormetastasis. The clinical study has also demonstrated that HGF has evidentbiologic effects on the promption of lung cancer metastasis. Theserium concentration of HGF and HGF expression in cancer tissues haveobvious association with the patient prognosis. That is to say, HGFmay be taken as a independent prognosis factor in lung cancer patients.