Thrombopoietin promotes angiogenesis and disease progression in patients with multiple myeloma

Multiple myeloma (MM) progression closely depends on bone marrow (BM) angiogenesis. Several factors sustain angiogenesis, including cytokines, growth factors, and cell-to-cell interactions. Herein, we found that BM thrombopoietin (TPO) supports angiogenesis and disease progression in MM. Patients with MM at different progression phases have higher levels of BM and circulating TPO than monoclonal gammopathy of undetermined significance/smoldering MM patients, suggesting that TPO correlates with disease progression and prognosis. Endothelial cells from monoclonal gammopathy of undetermined significance (MGECs) and endothelial cells from MM (MMECs) patients express TPO receptor, and the TPO treatment triggers their angiogenic capabilities in vitro. Indeed, TPO-treated MGECs and MMECs show enhanced angiogenesis on Matrigel and spontaneous cell migration and chemotaxis by acting as a chemotactic agent. TPO also has an angiogenic activity in vivo in the chorioallantoic membrane assay system. Finally, TPO treatment increases the release of active matrix metalloproteinase (MMP)-9 and MMP-2 in MGECs and of MMP-2 in MMECs and affects the balance between angiogenic/antiangiogenic factors in the MM BM. Our results support the angiogenic activity of TPO, and suggest that it may have a critical role in promoting the angiogenic switch during MM progression. Accordingly, TPO may be envisaged as a new angiogenic and prognostic factor in MM patients.