Abstract
Angiogenesis is the formation of new blood vessels from the existing vasculature and is necessary for tumor growth. Syndecan-2 (S2) is highly expressed in the microvasculature of mouse gliomas. When S2 expression was down-regulated in mouse brain microvascular endothelial cells (MvEC), this inhibited cell motility and reduced the formation of capillary tube-like structures in vitro. Pro-angiogenic growth factors and enzymes up-regulated during glioma tumorigenesis stimulated shedding of the S2 ectodomain from endothelial cells in vitro. The effect of shed S2 on angiogenic processes was investigated by incorporating recombinant S2 ectodomain (S2ED) into in vitro angiogenesis assays. S2ED promoted membrane protrusion, migration, capillary tube formation, and cell-cell interactions. We therefore propose that S2 is necessary for angiogenesis of MvEC, proangiogenic factors expressed during glioma progression regulate S2 shedding, and shed S2 ectodomain may increase endothelial cell angiogenic processes.
Highlights
Syndecan-2 is one of a family of transmembrane heparan sulfate proteoglycans
Syndecan-2 Is Expressed in the Microvasculature of Mouse Glioma Tumors—Immunohistochemistry demonstrated that S2 was highly expressed in gliomas propagated in mouse brain, in the vasculature of both the tumor (Fig. 1A, arrows) and normal brain tissue (Fig. 1A, arrowheads) but was generally not expressed in the normal brain parenchyma (Fig. 1A)
Syndecans have been investigated in some other types of cancers and in cancer cells [8, 10, 12], but this is the first report to indicate a role for S2 in glioma angiogenesis, a role for the shed ectodomain
Summary
Syndecan-2 Is Expressed in the Microvasculature of Gliomas and Regulates Angiogenic Processes in Microvascular Endothelial Cells*. When S2 expression was down-regulated in mouse brain microvascular endothelial cells (MvEC), this inhibited cell motility and reduced the formation of capillary tube-like structures in vitro. Pro-angiogenic growth factors and enzymes up-regulated during glioma tumorigenesis stimulated shedding of the S2 ectodomain from endothelial cells in vitro. We propose that S2 is necessary for angiogenesis of MvEC, proangiogenic factors expressed during glioma progression regulate S2 shedding, and shed S2 ectodomain may increase endothelial cell angiogenic processes. The mechanisms that regulate S2 expression and distribution during tumorigenesis and angiogenesis have not been described, but S1 and S4 can be shed from the cell surface, resulting in soluble ectodomains [2, 3]. We propose that S2 shedding that is regulated by pro-angiogenic growth factors and enzymes results in a soluble ectodomain that promotes angiogenic processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
