Premium
Expression of membrane type 1 matrix metalloproteinase (MT1‐MMP) in A2058 melanoma cells is associated with MMP‐2 activation and increased tumor growth and vascularization
Author(s) -
Sounni Nor Eddine,
Baramova Eugenia N.,
Munaut Carine,
Maquoi Erik,
Frankenne Francis,
Foidart JeanMichel,
Noël Agnès
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/ijc.10134
Subject(s) - matrix metalloproteinase , plasmin , metalloproteinase , transfection , biology , tumor progression , cancer research , melanoma , gelatinase a , matrilysin , microbiology and biotechnology , chemistry , cell culture , biochemistry , enzyme , gene , genetics
Membrane‐type metalloproteinase‐1 (MT1‐MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro‐MMP‐2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP‐2 activation that yields to the mature form is less understood and could involve an autocatalytic process and/or the activity of the plasminogen/plasmin system. Human melanoma A2058 cells, which express MMP‐2 only in its pro‐form, were used to determine the role of MT1‐MMP during pericellular proteolysis and tumor progression. The induction of MT1‐MMP overexpression by MT1‐MMP cDNA transfection initiated the first step of MMP‐2 activation. We provide evidence that a cooperation between the plasminogen/plasmin system and MT1‐MMP endowed the cells with the ability to fully activate MMP‐2 and with enhanced invasive properties in vitro . When injected subcutaneously in nude mice, MT1‐MMP expressing clones induced rapid tumor growth and high tumor vascularization, while the control clones were poorly or not tumorigenic. Our data provide the first demonstration, in an experimental model, that MT1‐MMP expression by tumor cells promotes tumor vascularization. © 2001 Wiley‐Liss, Inc.