title: Cell surface glypicans are low-affinity endostatin receptors.
abstract: Endostatin, a collagen XVIII fragment, is a potent anti-angiogenic protein. We sought to identify its endothelial cell surface receptor(s). Alkaline phosphatase- tagged endostatin bound endothelial cells revealing two binding affinities. Expression cloning identified glypican, a cell surface proteoglycan as the lower-affinity receptor. Biochemical and genetic studies indicated that glypicans' heparan sulfate glycosaminoglycans were critical for endostatin binding. Furthermore, endostatin selected a specific octasulfated hexasaccharide from a sequence in heparin. We have also demonstrated a role for endostatin in renal tubular cell branching morphogenesis and show that glypicans serve as low-affinity receptors for endostatin in these cells, as in endothelial cells. Finally, antisense experiments suggest the critical importance of glypicans in mediating endostatin activities.
authors.affiliation: Department of Medicine and the Cancer Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: V
authors.initials: V
authors.lastname: Jha
authors.forename: R
authors.initials: R
authors.lastname: Ramchandran
authors.forename: A
authors.initials: A
authors.lastname: Karihaloo
authors.forename: L
authors.initials: L
authors.lastname: Tsiokas
authors.forename: B
authors.initials: B
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Dhanabal
authors.forename: J I
authors.initials: JI
authors.lastname: Hanai
authors.forename: G
authors.initials: G
authors.lastname: Venkataraman
authors.forename: Z
authors.initials: Z
authors.lastname: Shriver
authors.forename: N
authors.initials: N
authors.lastname: Keiser
authors.forename: R
authors.initials: R
authors.lastname: Kalluri
authors.forename: H
authors.initials: H
authors.lastname: Zeng
authors.forename: D
authors.initials: D
authors.lastname: Mukhopadhyay
authors.forename: R L
authors.initials: RL
authors.lastname: Chen
authors.forename: A D
authors.initials: AD
authors.lastname: Lander
authors.forename: K
authors.initials: K
authors.lastname: Hagihara
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: R
authors.initials: R
authors.lastname: Sasisekharan
authors.forename: L
authors.initials: L
authors.lastname: Cantley
authors.forename: V P
authors.initials: VP
authors.lastname: Sukhatme
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism*; D043170:Collagen Type XVIII; D006224:Cricetinae; D043169:Endostatins; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D013431:Sulfates / Q000378:metabolism / Q000494:pharmacology
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D009844:Oligosaccharides; D010446:Peptide Fragments; D013431:Sulfates; D006493:Heparin; D003094:Collagen