Biology Reference
In-Depth Information
Chapter 7
The Role of Matrix Metalloproteinases
in Cellular Invasion and Metastasis
Elena I. Deryugina and James P. Quigley
Abstract Within the last two decades of research, the accumulated evidence
unequivocally demonstrates that proteolytic degradation and modification of
ECM proteins and proteolytic remodeling of stromal tissue play critical roles in
cell invasion. With regard to cancer biology, a particular class of proteolytic
enzymes, i.e., matrix metalloproteinases (MMPs), is considered highly important
in facilitating overall tumor progression and metastasis. As the metastatic cascade
represents a continuum of distinct steps, some of which appear to be rate-limiting,
the contribution of select MMPs at different stages of malignant disease could be
appreciated. Thus, secreted MMPs such as MMP-9 coming from nontumor cells
have been functionally linked to tumor progression, while other MMPs have been
shown to be potent in cell-cell contact dissolutions during the early epithelial-
to-mesenchymal transitions. The membrane-tethered MMPs such as MT1-MMP
appear to govern directional invasion of tumor cells across basement membranes
into surrounding collagen-enriched stroma. However, the identification of MMPs
which preferentially facilitate the later steps of the metastatic cascade, especially
the transition from micrometastases to macrometastases, remains an unanswered
issue. In addition, progress in cancer stem cell (CSC) biology, including the for-
mation of the premetastatic and vascular niches and mechanisms of CSC traffick-
ing, has indicated a high potential of MMP involvement. This review is focused
mostly on recent advances in our understanding of MMP physiology in meta-
static spread, but also provides an outlook on the experimental findings which
paved the ground for newly developed concepts and hypotheses about the roles of
MMPs in cancer progression especially in regard to stromal tissue and matrix
remodeling.
E.I. Deryugina (
*
) and J.P. Quigley
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
e-mail: deryugin@scripps.edu; jquigley@scripps.edu
