title: 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.
authors.affiliation: Hematology Department, University Hospital of Heraklion, PO Box 1352, 71110, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Tsirakis
authors.forename: Parascevi
authors.initials: P
authors.lastname: Roussou
authors.forename: Constantina A
authors.initials: CA
authors.lastname: Pappa
authors.forename: Anna
authors.initials: A
authors.lastname: Kolovou
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Vasilokonstantaki
authors.forename: Ioannis
authors.initials: I
authors.lastname: Miminas
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kyriakaki
authors.forename: Athanasios
authors.initials: A
authors.lastname: Alegakis
authors.forename: Michael G
authors.initials: MG
authors.lastname: Alexandrakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000097:blood* / Q000150:complications; D001862:Bone Resorption; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000150:complications; D009389:Neovascularization, Pathologic; D010010:Osteoclasts / Q000378:metabolism
chemical_list: C515429:CCL3 protein, human; D054405:Chemokine CCL3; C066855:HGF protein, human; D020382:Interleukin-18; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor