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[基质金属蛋白酶-9及其mRNA在胃癌中的表达及其与血管生成的相关性]

[Expression of MMP-9 and MMP-9 mRNA in gastric carcinoma and its correlation with angiogenesis].

作者信息

Wang Lu, Zhang Li-hong, Li Yu-lin, Li Yi-lei, Liu Zhan

机构信息

Department of Pathology, Basic Medical School, Jilin University, Changchun 130021, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2003 May 10;83(9):782-6.

PMID:12899759
Abstract

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.

CONCLUSION

Gastric cancer cells have the ability to produce and secret MMP-9 which can promote the invasion and metastasis of the neoplasm.

摘要

目的

探讨基质金属蛋白酶-9(MMP-9)及其mRNA在胃癌组织和细胞系中的表达,以及与胃癌侵袭、转移和血管生成的相关性。

方法

收集74例手术切除的人胃癌标本,培养人低分化胃癌BGC823细胞系。采用苏木精-伊红染色、免疫组织化学、原位杂交及酶谱法检测MMP-9、MMP-9 mRNA、CD34、α-平滑肌肌动蛋白(α-SMA)、血管内皮生长因子受体-1(VEGFR-1)、血管内皮生长因子受体-2(VEGFR-2)的表达。进行侵袭实验观察穿透基质胶的细胞数。分析MMP-9及其mRNA表达与临床参数的关系。

结果

胃癌组织中MMP-9表达阳性率为77.03%(57/74)。大部分MMP-9阳性细胞位于侵袭区域。74例胃癌的平均微血管密度(MVD)为73.76±11.50/200视野。MMP-9阳性组MVD为75.46±10.98,MMP-9阴性组为68.08±11.71(P<0.05)。胃癌组织中MMP-9 mRNA表达阳性率为72.97%(54/74)。MMP-9及其mRNA的表达与胃癌的侵袭、分化及淋巴结状态密切相关;MVD与胃癌的侵袭和淋巴结状态密切相关。所有BGC823细胞MMP-9、MMP-9 mRNA、VEGFR-2阳性,VEGFR-1阴性。MMP-9抗体组侵袭BGC823细胞数为(18±4)/400视野,对照组为(69±5)/400视野。培养皿中培养的BGC823细胞稳定表达MMP-2和MMP-9的酶原。I型胶原表面培养的BGC823细胞表达更多的MMP-2酶原和活性MMP-2。当BGC823细胞与血管内皮生长因子(VEGF)孵育时,MMP-9酶原含量随VEGF剂量依赖性增加。

结论

胃癌细胞具有产生和分泌MMP-9的能力,MMP-9可促进肿瘤的侵袭和转移。

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