Journal
MATRIX BIOLOGY
Volume 44-46, Issue -, Pages 94-112Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2015.04.004
Keywords
Matrix metalloproteinase; Tissue inhibitor of metalloproteinases; Tumor angiogenesis; Tumor cell intravasation and metastasis; Tumor-associated neutrophils; Tumor-associated macrophages; Vascular endothelial growth factor; Epidermal growth factor receptor
Categories
Funding
- National Institutes of Health (NIH) [R01CA55852, R01CA105412, R01CA129484]
- NIH [HL07695, 5T32HL07195-31, 5T32CA077109]
- American Heart Association Fellowship [0225103Y]
- Human Diversity and Re-Entry Award from NIH/NCI
- NIH/National Center for Research Resources/Scripps Translational Science Institute [UL1 RR025774, UL1 TR000109-05]
- Danish National Research Foundation
- Danish Cancer Society
- University of Aarhus
- Max Kade Foundation
- Fund for Scientific Research of Flanders
- University of Zurich
- Swiss National Science Foundation for Prospective Researches
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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. (C) 2015 Published by Elsevier B.V.
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