title: Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma.
abstract: Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.
authors.affiliation: Department of Hematology, University Hospital of Heraklion, Crete, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Tsirakis
authors.forename: Constantina A
authors.initials: CA
authors.lastname: Pappa
authors.forename: Peggy
authors.initials: P
authors.lastname: Kanellou
authors.forename: Maria A
authors.initials: MA
authors.lastname: Stratinaki
authors.forename: Athina
authors.initials: A
authors.lastname: Xekalou
authors.forename: Fotios E
authors.initials: FE
authors.lastname: Psarakis
authors.forename: George
authors.initials: G
authors.lastname: Sakellaris
authors.forename: Athanasios
authors.initials: A
authors.lastname: Alegakis
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
authors.forename: Michael G
authors.initials: MG
authors.lastname: Alexandrakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000098:blood supply / Q000473:pathology; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000097:blood / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000502:physiology*; D012259:Ribonuclease, Pancreatic / Q000097:blood / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000097:blood / Q000502:physiology*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D001613:beta 2-Microglobulin; C095477:platelet-derived growth factor AB; D016222:Fibroblast Growth Factor 2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic