Rapid clearance of the circulating metastatic factor autotaxin by the scavenger receptors of liver sinusoidal endothelial cells.
Autotaxin, also known as NPP2 (nucleotide pyrophosphatase/phosphodiesterase 2), is a secreted lysophospholipase-D that generates lysophosphatidic acid and thereby promotes the metastatic and invasive properties of tumor cell as well as angiogenesis. We show here that, in mice, NPP2 is cleared from the circulation within minutes and is retained by the liver sinusoidal endothelial cells (LSECs). The binding of NPP2 to isolated LSECs resulted in its degradation and could be competed for with ligands of the scavenger receptor family. Our finding that circulating NPP2 has a rapid turnover has important implications for its development as an anti-cancer target.
Jansen
Silvia
S
Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium.
Andries
Maria
M
Vekemans
Katrien
K
Vanbilloen
Hubert
H
Verbruggen
Alfons
A
Bollen
Mathieu
M
D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000098:blood supply*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009097:Multienzyme Complexes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009362:Neoplasm Metastasis / Q000503:physiopathology* / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000502:physiology; D043264:Phosphodiesterase I / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010727:Phosphoric Diester Hydrolases / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011755:Pyrophosphatases / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D000099189:Lysophospholipase D
D005557:Formaldehyde; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D051116:Receptors, Scavenger; D012710:Serum Albumin, Bovine; D000099189:Lysophospholipase D; C044105:formaldehyde-serum albumin; C029180:methylated bovine serum albumin