Abstract
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.
2009 Elsevier Ireland Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured / metabolism
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Endothelial Cells / metabolism*
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Formaldehyde / pharmacology
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Humans
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Injections, Intravenous
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Liver / blood supply*
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Male
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Metabolic Clearance Rate
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Mice
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Multienzyme Complexes / administration & dosage
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Multienzyme Complexes / blood
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Multienzyme Complexes / pharmacokinetics*
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Neoplasm Metastasis / physiopathology*
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Neoplasm Metastasis / prevention & control
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Neoplasm Proteins / administration & dosage
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Neoplasm Proteins / blood
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Neoplasm Proteins / pharmacokinetics*
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Neoplasm Proteins / physiology
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Phosphodiesterase I / administration & dosage
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Phosphodiesterase I / blood
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Phosphodiesterase I / pharmacokinetics*
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Phosphoric Diester Hydrolases / administration & dosage
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Phosphoric Diester Hydrolases / blood
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Phosphoric Diester Hydrolases / pharmacokinetics*
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Pyrophosphatases / administration & dosage
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Pyrophosphatases / blood
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Pyrophosphatases / pharmacokinetics*
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Rats
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Rats, Wistar
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Receptors, Scavenger / antagonists & inhibitors
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Receptors, Scavenger / metabolism*
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Serum Albumin, Bovine / pharmacology
Substances
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Multienzyme Complexes
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Neoplasm Proteins
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Receptors, Scavenger
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formaldehyde-serum albumin
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methylated bovine serum albumin
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Formaldehyde
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Serum Albumin, Bovine
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Phosphoric Diester Hydrolases
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Phosphodiesterase I
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alkylglycerophosphoethanolamine phosphodiesterase
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Pyrophosphatases