Activation of the precursor of gelatinase A/72 kda type IV collagenase/MMP‐2 in lung carcinomas correlates with the expression of membrane‐type matrix metalloproteinase (MT‐MMP) and with lymph node metastasis

Abstract

We have identified a novel membrane-type matrix metalloproteinase (MT-MMP) expressed on the cell surface and inducing activation of pro-gelatinase A in vitro. In this study, we further examined the possibility that MT-MMP is the activator of pro-gelatinase A in tumors as well as in vitro. Expression of MT-MMP mRNA was analyzed by Northern blotting in 58 cases of human lung carcinomas. MT-MMP mRNA expression was increased in tumor tissues compared with adjacent normal tissues. The ratio of MT-MMP mRNA levels in tumor/normal tissues (T/N ratio) was 3.19 +/- 1.62 in 29 cases of adenocarcinoma, 3.09 +/- 1.44 in 24 cases of squamous cell carcinoma, 4.40 +/- 0.47 in 3 cases of large cell carcinoma and 3.63 +/- 2.11 in 2 cases of small cell carcinoma, respectively. Activated gelatinase A, as detected by gelatin zymography, was also predominant in tumors compared with normal tissue counterparts, though the difference in mRNA levels was not significant. The activation ratio of gelatinase A in tumor vs. normal tissues correlated well with that of MT-MMP mRNA expression and with lymph node metastases. Our findings suggest that MT-MMP is indeed the tumor-specific activator of pro-gelatinase A in lung carcinomas and is important to initiate invasion of basement membranes.

Characteristics of primary care physicians and their practices associated with mammography rates for older women

“…Immunoreactivity for MMP-2 was correlated significantly with Masaoka clinical stage, and MMP-2 expression was correlated with the degree of malignant behavior of the thymoma and may be an indicator for distinguishing invasive thymoma from noninvasive thymoma. MMP-2 protein reportedly is correlated with poor prognostic variables in a variety of malignancies, such as breast, 15,16 lung, 17,18 stomach, 19 and head and neck carcinomas. 20 It was long been believed that TIMPs suppressed tumor invasion by inhibiting MMPs in experimental and clinical studies.…”

Cell surface binding and activation of gelatinase A induced by expression of membrane‐type‐1‐matrix metalloproteinase (MT1‐MMP)

“…MT1-MMP is overexpressed in malignant tumor tissues, including lung and stomach carcinomas that contain activated gelatinase A. This suggests that MT1-MMP is associated with the activation of progelatinase A in these tumor tissues [14,16,17]. MT1-MMP expression has been detected in HT-1080 cells treated with TPA and MDA-MB-231 cells stimulated with concanavalin A, which induce progelatinase A activation [18,19].…”

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation

“…1363-1371 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.1806, available online at http://www.idealibrary.com on http://www.bjcancer.com aminoterminal domain for the expression of activity (Tryggvason et al, 1987). The urokinase type plasminogen activator (uPA) -plasmin system (Mazzieri et al, 1997) and membrane type MMP-1 (MT1-MMP, MMP-14) (Sato et al, 1994;Tokuraku et al, 1995) have been suggested to represent physiological mechanisms for the control of MMP-2 and MMP-9 activity. Recent studies have shown that human trypsin-2 is more potent than plasmin and other serine proteinases in activating several MMPs, including MMP-2 and MMP-9 (Sorsa et al, 1997), and that downregulation of trypsin-2 expression and activity in colon cancer cells is associated with decreased proMMP-9 activation (Lukkonen et al, 2000).…”