Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature.
Metastasis is a distinct stage of cancer progression that requires the development of angiogenic blood vessels serving as conduits for tumor cell dissemination. An accumulated body of evidence indicates that metastasis-supporting neovasculature should possess certain structural characteristics allowing for the process of tumor cell intravasation, an active entry of cancer cells into the vessel interior. It appears that the development of tumor vessels with lumens of a distinctive size and support of these vessels by a discontinuous pericyte coverage constitute critical microarchitectural requirements to: (a) provide accessible points for vessel wall penetration by primary tumor cells; (b) provide enough lumen space for a tumor cell or cell aggregate upon intravasation; and (c) allow for sufficient rate of blood flow to carry away intravasated cells from the primary tumor to the next, proximal or distal site. This review will primarily focus on the functional roles of matrix metalloproteinases (MMPs), which catalytically trigger the development of an intravasation-sustaining neovasculature at the early stages of tumor growth and are also required for the maintenance of a metastasis-supporting state of blood vessels at later stages of cancer progression.
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States. Electronic address: deryugin@scripps.edu.
Elena I
EI
Deryugina
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States. Electronic address: jquigley@scripps.edu.
James P
JP
Quigley
D000818:Animals; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases
Epidermal growth factor receptor; Matrix metalloproteinase; Tissue inhibitor of metalloproteinases; Tumor angiogenesis; Tumor cell intravasation and metastasis; Tumor-associated macrophages; Tumor-associated neutrophils; Vascular endothelial growth factor