Autocrine Mechanism Of Vascular Endothelial Growth Factor Promoting Invasion Of Lung Cancer Cell

Objective: The high dead rate of malignant tumor mainly results from its local infiltration and metastasis in which VEGF and MMP-9 play important roles. This trial studies the relationship of VEGF and MMP-9 to detect an autocrine mechanism of VEGF promoting invasion of lung cancer cell and wish to provide some theories for anti-VEGF therapy of tumor. Methods: Immunohistochemistry was used to examine the expression of VEGF ,MMP-9 and iMVD in 45 resected speciments of lung cancer. And then the relationship between the expression levels of either VEGF or MMP-9 and clinicopathological factors was evaluated. In addition, lung adenocarcinoma cells of A549 line were cultured in serum-free RPMI1640 with or without rhVEGF165, then immunocytochemistry and invasion test were used to investigate the influence of VEGF on expression of MMP-9 and the invasion of A549 cells. Results: (1) The positive rates of VEGF and MMP-9 in lung cancer tissue were respectively 64.4%(29/45)and 60%(27/45). No statistically significant difference was observed between expression of either VEGF or MMP-9 and tumor diameter, lymph node metastasis, pathological stage and type(P>0.05). iMVD was 31.36±11.91/×400 in VEGF-negative tumors and 45.58±15.60/×400 in VEGF-positive tumors , between which there was statistically significant difference ( P<0.05 ) . iMVD in MMP-9-positive tumor(s44.64±16.41/×400) was significant higher than that in MMP-9-negative tumors(31.13±9.41/×400)(P<0.05). The expression of VEGF and MMP-9 was significantly associated (C=0.471>0.4 , P<0.001). (2) A549 cells incubated with 10ng/ml rhVEGF165 were examinated no expression of MMP-9 at 6-hour and 36-hour and feeble positive expression at 12- hour and 24-hour.But A549 cells incubated with 30ng/ml rhVEGF165 , feeble positive expression of MMP-9 was examinated at 6-hour and 24-hour , strong positive expression at 12-hour and negative expression at 36-hour. Feeble positive expression of MMP-9 was examinated only at 24- hour in A549 cells of control group added with PBS. (3) The number of invasive cells was 54.7±5.2/×400 and 2.7±2.1/×400 respectively in the groups with or without rhVEGF165 200ng/ml, and the difference was statistically significant(P<0.001). Conclusions: (1) Either VEGF or MMP-9 expression is significantly correlative with iMVD. There is significant correlation between VEGF and MMP-9 expression in lung cancer tissue, and both VEGF and MMP-9 possibly take part in the angiogenesis of tumor. (2) VEGF can induce the expression of MMP-9 in A549 cells with time-dose dependence. (3) VEGF can promote the invasion of A549 cells. (4) There is an autocrine mechanism in lung cancer cell and VEGF can induce the expression of MMP-9 of lung cancer cell to promote its infitration and metastasis.