© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1260-1270, Copyright © 1997 by Oxford University Press
AF Chambers and LM Matrisian
Metastatic spread of cancer continues to be the greatest barrier to cancer
cure. Understanding the molecular mechanisms of metastasis is crucial for
the design and effective use of novel therapeutic strategies to combat
metastases. One class of molecules that has been repeatedly implicated in
metastasis is the matrix metalloproteinases (MMPs). In this review, we
re-examine the evidence that MMPs are associated with metastasis and that
they make a functional contribution to the process. Initially, it was
believed that the major role of MMPs in metastasis was to facilitate the
breakdown of physical barriers to metastasis, thus promoting invasion and
entry into and out of blood or lymphatic vessels (intravasation,
extravasation). However, recent evidence suggests that MMPs may have a more
complex role in metastasis and that they may make important contributions
at other steps in the metastatic process. Studies using intravital
videomicroscopy, as well as experiments in which levels of MMPs or their
inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are
manipulated genetically or pharmacologically, suggest that MMPs are key
regulators of growth of tumors, at both primary and metastatic sites. On
the basis of this evidence, a new view of the functional role of MMPs in
metastasis is presented, which suggests that MMPs are important in creating
and maintaining an environment that supports the initiation and maintenance
of growth of primary and metastatic tumors. Further clarification of the
mechanisms by which MMPs regulate growth of primary and metastatic tumors
will be important in the development of novel therapeutic strategies
against metastases.
REVIEWS
Changing views of the role of matrix metalloproteinases in metastasis
Department of Oncology, University of Western Ontario, and London Regional Cancer Centre, Canada. achambers@lrcc.on.ca
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