[Expression of MMP-9 and MMP-9 mRNA in gastric carcinoma and its correlation with angiogenesis].
OBJECTIVE
To investigate the expression of MMP-9 and MMP-9 mRNA in the tissue and cell line of the gastric carcinoma and its correlation with invasion, metastasis and angiogenesis of the cancer.


METHODS
Seventy-four specimens of resected human gastric carcinoma were collected. Human lowly differentiated gastric carcinoma cells of BGC823 line were cultured. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, and zymography were used to examine the expression of MMP-9, MMP-9 mRNA, CD34, alpha-SMA, VEGFR-1, VEGFR-2. Invasion test was made to observe the number of cells penetrating the Matrigel. The relationship between the expression of MMP-9 and MMP-9 mRNA and the clinical parameters was analyzed.


RESULTS
The positive rate of MMP-9 expression was 77.03% in gastric carcinoma tissues (57/74). Most of the MMP-9 positive cells were located at the invasive areas. The average microvascular density (MVD) of the 74 cases of gastric carcinoma was 73.76 +/- 11.50/200 x visual field. MVD was 75.46 +/- 10.98 in the MMP-9 positive group and was 68.08 +/- 11.71 in the MMP-9 negative group (P < 0.05). The positive rate of MMP-9 mRNA expression was 72.97% in the gastric carcinoma tissues (54/74). The expressions of MMP-9 and its mRNA were closely related to invasion, differentiation and lymph nodes status of the gastric carcinoma; MVD was closely related to the invasion and lymph nodes status of the gastric carcinoma. All BGC823 cells were MMP-9, MMP-9 mRNA, VEGFR-2 positive and VEGFR-1 negative. The number of invasive BGC823 cells was (18 +/- 4)/400 x in the MMP-9 antibody group and was (69 +/- 5)/400 x in the control group. BGC823 cells cultivated in culture dishes expressed the proenzyme of MMP-2 and MMP-9 stably. BGC823 cells cultivated on the surface of type I collagen expressed more MMP-2 proenzyme and active MMP-2. When BGC823 cells were incubated with VEGF, the content of MMP-9 proenzyme was increased by VEGF dose-dependently.


CONCLUSIONS
Gastric cancer cells have the ability to produce and secret MMP-9 which can promote the invasion and metastasis of the neoplasm.
Wang
Lu
L
Department of Pathology, Basic Medical School, Jilin University, Changchun 130021, China.
Zhang
Li-hong
LH
Li
Yu-lin
YL
Li
Yi-lei
YL
Liu
Zhan
Z
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology* / Q000556:secondary; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D018952:Antigens, CD34; D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9