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Expression of tissue inhibitor of matrix metalloproteinase‐2 correlates with activation of matrix metalloproteinase‐2 and predicts poor prognosis in tongue squamous cell carcinoma
Author(s) -
Yoshizaki Tomokazu,
Maruyama Yumiko,
Sato Hiroshi,
Furukawa Mitsuru
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010120)95:1<44::aid-ijc1008>3.0.co;2-m
Subject(s) - matrix metalloproteinase , tissue inhibitor of metalloproteinase , immunohistochemistry , pathology , zymography , metastasis , activator (genetics) , tongue , medicine , gelatinase a , cancer research , cancer , receptor
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. © 2001 Wiley‐Liss, Inc.