title: Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra-bone marrow involvement in multiple myeloma patients.
abstract: The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P < 0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM.
authors.affiliation: Section of Haematology, Department of Biomedical Sciences, University of Ferrara, Ferrara, Italy. sse@dns.unife.it
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.forename: Alessia
authors.initials: A
authors.lastname: Tieghi
authors.forename: Maria
authors.initials: M
authors.lastname: Ciccone
authors.forename: Letizia Zenone
authors.initials: LZ
authors.lastname: Bragotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.forename: Matteo
authors.initials: M
authors.lastname: Della Porta
authors.forename: Barbara
authors.initials: B
authors.lastname: Castagnari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Carroccia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guerra
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D016022:Case-Control Studies; D003404:Creatinine / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000276:immunology*; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis*; D055293:Receptors, Urokinase Plasminogen Activator; D053668:Syndecan-1; D053667:Syndecans; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D019002:CD56 Antigen; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D001613:beta 2-Microglobulin; D003404:Creatinine; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1