TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell-matrix interactions on collagen.
The TEM8 gene is selectively expressed in tumor versus normal blood vessels, though its function in endothelial cell biology is not known. Towards the goal of clarifying this function, we tested whether TEM8 overexpression, or blocking TEM8's function with a dominant negative protein, would modulate endothelial cell activities. We found that TEM8-expressing endothelial cells migrated at a rate 3-fold greater than control cells in a monolayer denudation assay. Also, the addition of recombinant TEM8 extracellular domain (TEM8-ED) specifically inhibited both chemokinetic and chemotactic migration on collagen in the denudation and Boyden chamber assays, respectively. The TEM8-ED binds preferentially to collagen, and TEM8 expression enhanced endothelial adhesion to collagen 3-fold; the latter response was antagonized by the TEM8-ED. Consistent with the TEM8-ED acting as a dominant negative inhibitor of endogenously expressed protein were data showing that the TEM8-ED had no effect on the activation of beta1 integrin. TEM8 protein is present in human umbilical vein in situ and is expressed in low passage HUVEC in vitro. TEM8 protein expression in HUVEC was increased 5-fold by the initiation of tube formation, correlating expression of TEM8 with the angiogenic response. Taken together, these results indicate that TEM8 plays a positive role in endothelial cell activities related to angiogenesis.
Hotchkiss
Kylie A
KA
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Basile
Cheryl M
CM
Spring
Simone C
SC
Bonuccelli
Gloria
G
Lisanti
Michael P
MP
Terman
Bruce I
BI
D000273:Adipose Tissue / Q000098:blood supply; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004822:Epididymis; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D018919:Neovascularization, Physiologic; D016133:Polymerase Chain Reaction; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014471:Umbilical Veins
C473287:ANTXR1 protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D003094:Collagen