چكيده فارسي :
Functions of individual matrix metalloproteinases
(MMPs) differentially expressed by tumor cells and stromal
cells, are finely regulated by their spatial as well as
temporal interactions with distinct cellular and extracellular
components of the tumor microenvironment and also distant
pre-metastatic sites. Certain aspects of MMP involvement
in tumor metastasis such as tumor-induced angiogenesis, tumor
invasion, and establishment of metastatic foci at the secondary
site, have received extensive attention that resulted in
an overwhelming amount of experimental and observational
data in favor of critical roles of MMPs in these processes. In
particular, dependency of tumor angiogenesis on the activity
of MMPs, especially that of MMP-9, renders this step possibly
the most effective target of synthetic MMP inhibitors.
MMP functioning in other stages of metastasis, including
the escape of individual tumor cells from the primary tumor,
their intravasation, survival in circulation, and extravasation
at the secondary site, have not yet received enough consideration,
resulting in insufficient or controversial data. The major
pieces of evidence that are most compelling and clearly determine
the role and involvement of MMPs in the metastatic
cascade are provided by molecular genetic studies employing
knock-out or transgenic animals and tumor cell lines, modified
to overexpress or downregulate a specific MMP. Findings
from all of these studies implicate different functional
mechanisms for both tumor and stromal MMPs during distinct
steps of the metastatic cascade and indicate that MMPs
can exhibit pro-metastatic as well as anti-metastatic roles
depending on their nature and the experimental setting
