Huang L W, Garrett A P, Bell D A, Welch W R, Berkowitz R S, Mok S C
Laboratory and Division of Gynecologic Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Gynecol Oncol. 2000 Jun;77(3):369-76. doi: 10.1006/gyno.2000.5806.
Matrix metalloproteinase-9 (MMP-9) can degrade gelatin and type IV collagen and is known to play an important role in tumor cell invasion across the basement membrane. The tissue inhibitor of metalloproteinase-1 (TIMP-1) is able to prevent activation of pro-MMP-9 and forms a 1:1 complex with the active form of MMP-9. The aim of the present study was to investigate the expression of MMP-9 and TIMP-1 in benign, borderline, and invasive epithelial ovarian tumors.
A total of 90 patients with epithelial ovarian tumor were treated at the Brigham and Women's Hospital and were used as the study population. Immunohistochemistry and in situ hybridization were performed to detect protein and mRNA expression of MMP-9 and TIMP-1.
In the 90 epithelial ovarian tumors tested, MMP-9 expression in tumor cells was found to be significantly enhanced in serous and mucinous ovarian carcinomas compared with benign and borderline tumors. We also observed the immunostaining of MMP-9 in stromal cells of benign, borderline, and invasive epithelial ovarian tumors. Moreover, the expression levels of TIMP-1 in tumor cells were significantly higher in borderline and invasive ovarian tumors than in benign tumors.
Using an in situ hybridization technique, we disclosed a direct correlation between the presence of mRNA and protein expression for both MMP-9 and TIMP-1. The present data suggest that high levels of MMP-9 protein in invasive epithelial ovarian carcinoma are strongly associated with tumor cell invasion. Enhanced expression of TIMP-1 protein in borderline and invasive tumors indicates that endogenous TIMP-1 protein may play a paradoxical role in ovarian tumor progression.
基质金属蛋白酶-9（MMP-9）可降解明胶和IV型胶原，已知其在肿瘤细胞穿过基底膜的侵袭过程中起重要作用。金属蛋白酶组织抑制剂-1（TIMP-1）能够阻止前MMP-9的激活，并与活性形式的MMP-9形成1:1复合物。本研究的目的是调查MMP-9和TIMP-1在良性、交界性和侵袭性上皮性卵巢肿瘤中的表达。
共有90例上皮性卵巢肿瘤患者在布莱根妇女医院接受治疗，并作为研究人群。采用免疫组织化学和原位杂交技术检测MMP-9和TIMP-1的蛋白和mRNA表达。
在检测的90例上皮性卵巢肿瘤中，发现浆液性和黏液性卵巢癌的肿瘤细胞中MMP-9表达较良性和交界性肿瘤显著增强。我们还观察到良性、交界性和侵袭性上皮性卵巢肿瘤的基质细胞中有MMP-9免疫染色。此外，交界性和侵袭性卵巢肿瘤的肿瘤细胞中TIMP-1表达水平显著高于良性肿瘤。
通过原位杂交技术，我们揭示了MMP-9和TIMP-1的mRNA与蛋白表达之间存在直接相关性。目前的数据表明，侵袭性上皮性卵巢癌中高水平的MMP-9蛋白与肿瘤细胞侵袭密切相关。交界性和侵袭性肿瘤中TIMP-1蛋白表达增强表明内源性TIMP-1蛋白可能在卵巢肿瘤进展中发挥矛盾的作用。
