Premium
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
Author(s) -
Tokuraku Masato,
Sato Hiroshi,
Murakami Sinya,
Okada Yasunori,
Watanabe Yoh,
Seiki Motoharu
Publication year - 1995
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/ijc.2910640513
Subject(s) - gelatinase a , matrix metalloproteinase , gelatinase , pathology , carcinoma , lymph node , collagenase , adenocarcinoma , biology , interstitial collagenase , metalloproteinase , basement membrane , cancer research , cancer , medicine , enzyme , biochemistry , genetics
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. © 1995 Wiley‐Liss, Inc.