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High level of MT‐MMP expression is associated with invasiveness of cervical cancer cells
Author(s) -
Gilles Christine,
Polette Myriam,
Piette Jacques,
Munaut Carine,
Thompson Erik W.,
Birembaut Philippe,
Foidart JeanMichel
Publication year - 1996
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/(sici)1097-0215(19960117)65:2<209::aid-ijc14>3.0.co;2-8
Subject(s) - matrix metalloproteinase , gelatinase a , biology , stromal cell , in vivo , cancer research , in situ hybridization , gelatinase , cell culture , lymph node , in vitro , immunohistochemistry , pathology , cancer cell , cancer , gene expression , immunology , medicine , gene , biochemistry , genetics , microbiology and biotechnology
MMP‐2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo . It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane‐associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF‐β, but its physiological regulation is still largely unresolved. MT‐MMP was recently discovered and described as a potential gelatinase‐A activator. In the present study, we investigated the expression of MT‐MMP (membrane‐type metalloproteinase) in cervical cancer cells both in vitro and in vivo . Comparing several in vitro ‐transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT‐MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT‐MMP expression in invasive cervical carcinoma and lymphnode metastases compared to its expression in non‐invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT‐MMP. Taken together, our results clearly correlated high level MT‐MMP expression with invasiveness, and thus suggested that MT‐MMP might play a crucial role in cervical tumor invasion. © 1996 Wiley‐Liss, Inc.