Recombinant CD44-HABD is a novel and potent direct angiogenesis inhibitor enforcing endothelial cell-specific growth inhibition independently of hyaluronic acid binding.
CD44 is the main cellular receptor for hyaluronic acid (HA). We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice. Here, we show that soluble recombinant CD44 HA-binding domain (CD44-HABD) acts directly onto endothelial cells by inhibiting endothelial cell proliferation in a cell-specific manner. Consequently, soluble recombinant CD44-HABD also blocked angiogenesis in vivo in chick and mouse, and thereby inhibited tumor growth of various origins at very low doses (0.25 mg/kg x day). The antiangiogenic effect of CD44 is independent of its HA-binding capacity, since mutants deficient in HA binding still maintain their antiangiogenic and antiproliferative properties. Recombinant CD44-HABD represents a novel class of angiogenesis inhibitors based on a cell-surface receptor.
Päll
Taavi
T
Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital F 46, Huddinge, 141 86 Huddinge, Sweden.
Gad
Annica
A
Kasak
Lagle
L
Drews
Monika
M
Strömblad
Staffan
S
Kogerman
Priit
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002645:Chickens; D005354:Fibrosarcoma; D005909:Glioblastoma; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma; D051379:Mice; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D006820:Hyaluronic Acid