| Autor: |
Manzo P; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy., Giudice V; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy.; Department of Medicine and Surgery, University of Salerno, 84081 Baronissi, Italy., Napolitano F; Department of Translational Medical Sciences, University of Naples 'Federico II', 80138 Naples, Italy., De Novellis D; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy.; Department of Medicine and Surgery, University of Salerno, 84081 Baronissi, Italy., Serio B; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy., Moscato P; Rheumatology Unit, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy., Montuori N; Department of Translational Medical Sciences, University of Naples 'Federico II', 80138 Naples, Italy., Selleri C; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', 84131 Salerno, Italy.; Department of Medicine and Surgery, University of Salerno, 84081 Baronissi, Italy. |
| Abstrakt: |
The microenvironment plays an essential role in multiple myeloma (MM) development, progression, cell proliferation, survival, immunological escape, and drug resistance. Mesenchymal stromal cells and macrophages release tolerogenic cytokines and favor anti-apoptotic signaling pathway activation, while the urokinase plasminogen activator receptor (uPAR) system contributes to migration through an extracellular matrix. Here, we first summarized the role of macrophages and the uPAR system in MM pathogenesis, and then we reported the potential therapeutic effects of uPAR inhibitors in a case series of primary MM-derived adherent cells. Our preliminary results showed that after uPAR inhibitor treatments, interleukein-6 (mean ± SD, 8734.95 ± 4169.2 pg/mL vs. 359.26 ± 393.8 pg/mL, pre- vs. post-treatment; p = 0.0012) and DKK-1 levels (mean ± SD, 7005.41 ± 6393.4 pg/mL vs. 61.74 ± 55.2 pg/mL, pre- vs. post-treatment; p = 0.0043) in culture medium were almost completely abolished, supporting further investigation of uPAR blockade as a therapeutic strategy for MM treatment. Therefore, uPAR inhibitors could exert both anti-inflammatory and pro-immunosurveillance activity. However, our preliminary results need further validation in additional in vitro and in vivo studies. |
