The collagen type XVIII endostatin domain is co-localized with perlecan in basement membranes in vivo.
The C-terminal globular endostatin domain of collagen type XVIII is anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. In contrast, many of its cell biological properties are still unknown. We systematically localized the mRNA of collagen type XVIII with the help of in situ hybridization (ISH) and detected it in epithelial and mesenchymal cells of almost all organ systems throughout mouse development. Light and electron microscopic immunohistochemistry (IHC) revealed that the endostatin domain is a widespread component of almost all epithelial basement membranes in all major developing organs, and in all basement membranes of capillaries and blood vessels. Furthermore, quantitative immunogold double labeling demonstrated a co-localization of 50% of the detected endostatin domain together with perlecan in basement membranes in vivo. We conclude that the endostatin domain of collagen type XVIII plays a role, even in early stages of mouse development, other than regulating angiogenesis. In the adult, the endostatin domain could well be involved in connecting collagen type XVIII to the basement membrane scaffolds. At least in part, perlecan appears to be an adaptor molecule for the endostatin domain in basement membranes in vivo.
Miosge
Nicolai
N
Zentrum Anatomie, Abteilung Histologie, Göttingen, Germany. nmiosge@gwdg.de
Simniok
Timo
T
Sprysch
Patricia
P
Herken
Rainer
R
D000818:Animals; D001485:Basement Membrane / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D043170:Collagen Type XVIII; D003627:Data Interpretation, Statistical; D043169:Endostatins; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism
D002135:Calcium-Binding Proteins; D043170:Collagen Type XVIII; D043169:Endostatins; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C084612:fibulin 2; C029967:nidogen; C071927:perlecan; D003094:Collagen