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Soluble urokinase‐type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra‐bone marrow involvement in multiple myeloma patients
Author(s) -
Rigolin Gian Matteo,
Tieghi Alessia,
Ciccone Maria,
Bragotti Letizia Ze,
Cavazzini Francesco,
Porta Matteo Della,
Castagnari Barbara,
Carroccia Rosanna,
Guerra Giovanni,
Cuneo Antonio,
Castoldi Gianluigi
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04176.x
Subject(s) - urokinase receptor , supar , multiple myeloma , bone marrow , biology , plasminogen activator , beta 2 microglobulin , plasma cell , cancer research , plasmin , microbiology and biotechnology , immunology , endocrinology , biochemistry , enzyme
Summary. 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 CD45 bright positivity ( P = 0·014). suPAR levels correlated positively with soluble serum CD138 ( P = 0·001), creatinine ( P = 0·001), beta 2 ‐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.