Soluble urokinase‐type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra‐bone marrow involvement in multiple myeloma patients

Abstract

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 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.

Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients

“…Strikingly, in our study, uPAR antigen levels in serum of STS patients were found to be highly and significantly associated with poor OS in Kaplan -Meier analyses and in multivariate Cox's regression analyses. This is in line with other studies that reported that high serum levels of soluble uPAR (suPAR) were significantly associated with worse survival in colorectal, prostate, ovarian and breast cancer, as well as in multiple myeloma (Sier et al, 1998;Brünner et al, 1999;Miyake et al, 1999;Stephens et al, 1999;Riisbro et al, 2002;Rigolin et al, 2003;Shariat et al, 2007) In contrast to cell-bound uPAR, which focuses uPA mediated plasmin formation to the cell surface, the role and source of suPAR remain to be clarified . Holst-Hansen et al (1999) demonstrated that the amount of suPAR released from breast cancer cell lines was directly correlated to the number of viable cells.…”

Role of flow cytometry in multiple myeloma and the prognostic significance of CD87 (uPAR) expression

“…Similarly, Rigolin et al [19] reported CD87 expression in all of their patients (n=49). On the other hand, Plesner et al [20] could not detect uPAR in any of their patients in a series including 10 cases.…”

“…Rigolin et al [19] determined an association between high CD87 expression and lytic bone lesions. However, we could not demonstrate such a correlation in our study.…”

“…The study by Hjertner et al [8] showed that uPAR expression depended on myeloma cell maturation and that immature myeloma cells had high expression levels. Rigolin et al [19] classified 49 patients into two groups according to CD87 expression. Patients with high CD87 expression also had high CD56, CD38, CD138 and high CD45 positivity.…”

“…Using flow cytometry, Rigolin et al [19] determined neoplastic cells expressing CD87 in all of the 49 MM patients included in their study. The highest CD87 expression was by CD45 (+) immature plasma cells; in addition, these cells displayed strong reactivity against CD138 and CD56, which are two important molecules for the cell adhesion process.…”