Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma

Abstract

Many cytokines possess variable roles in the pathogenesis of multiple myeloma. Macrophage inflammatory protein-1alpha (MIP-1alpha) is an osteoclast-activating factor with a major role in myeloma bone disease. The aim of the study was to examine its participation in the angiogenic process of the disease. We measured, by enzyme-linked immunosorbent assays, its serum levels in 56 newly diagnosed myeloma patients, in several skeletal grades and stages of the disease and in 25 healthy controls. Concurrently, we measured serum levels of the angiogenic cytokines basic-fibroblast growth factor, hepatocyte growth factor and interleukin-18. All the above cytokines were higher in myeloma patients (p < 0.001 for all cases) and were increasing in parallel with disease stage (p < 0.001 for all cases) and skeletal grade (p < 0.04 for MIP-1alpha and p < 0.001 for the other cases). Moreover, positive correlations between MIP-1alpha and all the angiogenic cytokines were noted (p < 0.001 for all cases). MIP-1alpha seems to be a predominant factor responsible for the enhancement of bone resorption and increased angiogenesis. The positive correlation between MIP-1alpha and the angiogenic chemoattractants supports the involvement of these factors in the biology of myeloma cell growth. Moreover, they could be used as possible therapeutic targets as well as markers of disease activity.

Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation

“…Elevated levels of cytokines have also been described in other hematological malignancies including chronic myeloid leukemia (CML), non-Hodgkin lymphoma, multiple myeloma and myelodysplastic syndromes. 11 , 12 , 13 , 14 , 15 , 16 Moreover, the high plasmatic levels of inflammatory cytokines are associated with the response of CML patients to tyrosine-kinase inhibitors and with the prognosis of the aforementioned hematological malignancies. 11 , 12 , 13 , 14 , 15 , 16 …”

HIF-2α Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1

“…Using microarray, we identified that the most highly upregulated gene following HIF-2a overexpression in LP-1 cells was the chemokine receptor CCR1. CCR1 has previously been suggested to play an important role in multiple myeloma with the levels of the CCR1 ligand CCL3 being elevated in the peripheral blood of multiple myeloma patients with advanced disease (43,44). Notably, CCL3 acts as a potent stimulus for the migration of multiple myeloma cells in vitro (45).…”

The insulin-like growth factor system in multiple myeloma: diagnostic and therapeutic potential

“…In MM patients, however, RANKL is overexpressed as OPG levels decrease, leading to a disturbed RANKL/OPG balance favoring bone resorption [136]. MM cells also produce MIP-1α, and increased MIP-1α serum levels correlate with lytic bone lesions in MM patients [137, 138]. In addition, the MM cells express and secrete factors that are able to suppress OB differentiation and activity.…”