Yoshizaki T, Maruyama Y, Sato H, Furukawa M
Department of Otolaryngology, School of Medicine, Kanazawa University, Kanazawa, Japan.
Int J Cancer. 2001 Jan 20;95(1):44-50. doi: 10.1002/1097-0215(20010120)95:1<44::aid-ijc1008>3.0.co;2-m.
Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to be essential for cell-mediated activation of MMP-2 and thus, the contribution of TIMP-2 to tumor invasion has remained controversial. This study was designed to analyze the role of TIMP-2 for activation of MMP-2 and its prognostic value in tongue squamous cell carcinoma (SCC). Expression of MMP-2, MT1-MMP and TIMP-2 protein was analyzed by immunohistochemistry, and their association with clinical factors was evaluated in 51 patients treated surgically for tongue SCC. Expression of MMP-2, MT1-MMP and TIMP-2 was significantly correlated with local and distant metastatic tumor recurrence and poor prognosis (MMP-2 and MT1-MMP, p < 0.0001; TIMP-2, p = 0.0002). Activation of MMP-2, analyzed by gelatin zymography in 17 fresh specimens, was remarkably associated with expression of MMP-2 (r = 0.779, p < 0.0001), MT1-MMP (r = 0.674, p < 0.0022) and TIMP-2 (r = 0.858, p < 0.0001). Increased expression of TIMP-2, as well as MMP-2 and MT1-MMP, was an important prognostic factor in patients with tongue SCC.
基质金属蛋白酶2（MMP - 2）在恶性肿瘤的侵袭和转移中起关键作用。膜型1 - MMP（MT1 - MMP）最初被鉴定为MMP - 2的激活剂。MMP - 2组织抑制剂（TIMP - 2）被鉴定为MMP - 2和MT1 - MMP的抑制剂。然而，据报道TIMP - 2对于细胞介导的MMP - 2激活至关重要，因此，TIMP - 2对肿瘤侵袭的作用一直存在争议。本研究旨在分析TIMP - 2在舌鳞状细胞癌（SCC）中对MMP - 2激活的作用及其预后价值。通过免疫组织化学分析MMP - 2、MT1 - MMP和TIMP - 2蛋白的表达，并在51例接受手术治疗的舌SCC患者中评估它们与临床因素的相关性。MMP - 2、MT1 - MMP和TIMP - 2的表达与局部和远处转移性肿瘤复发及预后不良显著相关（MMP - 2和MT1 - MMP，p < 0.0001；TIMP - 2，p = 0.0002）。在17个新鲜标本中通过明胶酶谱分析的MMP - 2激活与MMP - 2（r = 0.779，p < 0.0001）、MT1 - MMP（r = 0.674，p < 0.0022）和TIMP - 2（r = 0.858，p < 0.0001）的表达显著相关。TIMP - 2以及MMP - 2和MT1 - MMP的表达增加是舌SCC患者的重要预后因素。
