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Cell surface glypicans are low-affinity endostatin receptors.

  • Author(s): Karumanchi, SA
  • Jha, V
  • Ramchandran, R
  • Karihaloo, A
  • Tsiokas, L
  • Chan, B
  • Dhanabal, M
  • Hanai, JI
  • Venkataraman, G
  • Shriver, Z
  • Keiser, N
  • Kalluri, R
  • Zeng, H
  • Mukhopadhyay, D
  • Chen, RL
  • Lander, AD
  • Hagihara, K
  • Yamaguchi, Y
  • Sasisekharan, R
  • Cantley, L
  • Sukhatme, VP
  • et al.
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.

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