Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas

Abstract

BACKGROUND The 5‐year survival rate of patients with submucosal (sm) esophageal carcinoma continues to be much worse than that with intramucosal (m) lesions. The reasons are unclear, but matrix metalloproteinases (MMPs) and membrane type matrix metalloproteinases (MT‐MMPs) are known to be involved in degradation of extracellular matrix macromolecules associated with tumor cell invasion. Expression of these enzymes may have some relation to the difference in survival between patients with sm and m esophageal carcinomas. METHODS Surgical specimens from 148 primary esophageal squamous cell carcinomas were examined for expression of MMP‐1, 2, 3, 7, and 9; tissue inhibitor of MMP (TIMP)‐1 and 2; MT1‐MMP; and MT2‐MMP by immunohistochemical staining. The results were compared with tumor progression and other clinicopathologic parameters. Localization of gelatinase activity was also confirmed in carcinoma cells by in situ zymography. RESULTS Expression of MMP‐7 and 9, expression of MT1‐MMP, and gelatinase activity were elevated in the carcinomas, correlating with depth of tumor invasion. Percentages of positive sm cases were 44.0%, 51.9%, and 52.0%, respectively, significantly higher than for the m cases. Percentages of venous invasion positive cases were 61.9%, 65.1%, and 65.1%, respectively. CONCLUSIONS Expression of MMP‐7 and 9 and MT1‐MMP is closely associated with invasion depth and venous invasion in esophageal squamous cell carcinomas. Cancer 2000;88:2201–9. © 2000 American Cancer Society.

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

“…This has been shown in laryngeal carcinoma with MMP-13, 45 in oesophageal carcinoma with high MMP-7, MMP-9 and MT1-MMP expression levels 46 and in oral SCCs with high MMP-2 and MMP-9 30,47 and MMP-1, MMP-3 and MT1-MMP expression. 47 Invasive behavior of gastric carcinoma is associated with MT1-MMP expression 48 and bladder carcinoma with both MMP-2 and MT1-MMP expression.…”

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

“…Intriguingly, both MMPs were more highly expressed in the metastatic regions than in the primary regions of OSCC, and this pattern was quite prominent in gingival cancers. The increased expression of MMPs correlates with the proliferation and invasion of tumor cells (16)(17)(18)(19)(20)(21)(22)(23). The enhancement of MMP activity in cultured cells indicates increased metastatic potential (24)(25)(26).…”

2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption

“…During the process of degeneration, the IVD exhibits a progressive and significant reduction in height due to tissue resorption. Since collagen is the most abundant disc matrix protein, and since collagen molecules can be cleaved by only very few proteases, the group of collagen-degrading enzymes -the matrix metalloproteinases (MMPs) -have recently been attracting more and more attention [12,13,20,21,25,26,27,31,35]. MMP-1 is unique in degrading native, intact interstitial collagen (such as collagen I, II and III), while the two gelatinases (MMPs-2 and -9) cleave denatured collagen molecules and basement membrane collagen type IV.…”