title: Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders: correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism.
abstract: Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) system and the family of metalloproteinases (MMPs) catalyse the matrix degradation and remodelling processes characteristic of invasive malignant disorders. In a cohort of 50 patients with chronic myeloproliferative disorders (MPD) serum markers for collagen metabolism were compared to plasma levels of enzymes of the uPA and MMP system. Serum aminoterminal propeptide of type III procollagen (S-PIIINP) (P < 0.0001) concentration was significantly higher in the patients (median 3.7 micro g/L vs. 2.5 micro g/L) compared with controls. In a subgroup analysis comprising patients with myelofibrosis (MF), polycythaemia vera (PV) and essential thrombocythaemia (ET), respectively, S-PIIINP levels differed significantly with the highest values found in patients with MF (MF vs. PV vs. ET; P = 0.0027). Serum concentration of carboxyterminal telopeptide of type I collagen (S-ICTP) (P = 0.0006), reflecting type I collagen degradation, was significantly higher in patients compared with controls (median 4.0 micro g/L vs. 2.7 micro g/L). When comparing S-ICTP measurements between patient subgroups and controls there were only significantly higher values among MF and PV patients (MF vs. controls; P < 0.0001, PV vs. controls; P = 0.0016). A significant correlation between the marker for collagen synthesis (S-PIIINP) and degradation (S-ICTP) (r = 0.59; P < 0.0001) was demonstrated. A correlation analysis between serum markers for bone marrow remodelling processes (S-PIIINP, S-ICTP and S-hyaluronan) and plasma-soluble urokinase plasminogen receptor (suPAR) disclosed a significant relationship between suPAR and S-PIIINP (r = 0.48; P = 0.0009), S-hyaluronan (r = 0.56; P < 0.0001) and S-ICTP (r = 0.47; P = 0.0013), respectively. Plasma levels of MMP-2 and -9 were not correlated to serum markers for collagen metabolism. These findings suggest that enzymes of the uPA system might participate in the bone marrow remodelling processes characteristic of MPD.
authors.affiliation: Department of Haematology L, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark. mkh@dadlnet.dk
authors.forename: Morten Krogh
authors.initials: MK
authors.lastname: Jensen
authors.forename: Rikke
authors.initials: R
authors.lastname: Riisbro
authors.forename: Mads N
authors.initials: MN
authors.lastname: Holten-Andersen
authors.forename: Peter de Nully
authors.initials: Pde N
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003094:Collagen / Q000097:blood / Q000378:metabolism*; D024042:Collagen Type I; D024061:Collagen Type III / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000378:metabolism; D010455:Peptides / Q000097:blood; D011087:Polycythemia Vera / Q000097:blood; D055728:Primary Myelofibrosis / Q000097:blood; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013922:Thrombocytosis / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C524898:PLAUR protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C052929:collagen type I trimeric cross-linked peptide; D006820:Hyaluronic Acid; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator