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.

Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis

“…This indicates that MM patients who present with a high angiogenic status, translated to a high MVD count, run a 85% greater risk of death than MM patients with low angiogenic status at diagnosis. Several individual studies have demonstrated poor survival for MM patients with high MVD status [36,37,51,52,53,56,57,58,59,60,61,62,63]; our study based on a validated statistical methodology further strengthens this conclusion. More specifically, this meta-analysis, by integrating for the first time the existing data from individual reports, proves that that MVD can be considered as a surrogate marker of survival for MM patients as well as provide a novel, pooled estimation of the impact of angiogenesis in this disease.…”

“…Furthermore, many previous studies have demonstrated the clinical significance of angiogenesis in MM, and the majority of them have correlated the high MVD count with poor prognosis [36,37,51,52,53,54,55,56,57,58,59,60,61,62,63]. …”

Highly Expressed Integrin-α8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse

“…We investigated whether PDGFRA and PDGFRB has significant co-occurrence with ITGA8 using the cBioPortal genome database, and the results were consistent with our finding that increasing integrin-α8 expression induced PDGFRA and PDGFRB mRNA expression. PDGFR signaling has been thoroughly investigated in cancer, including MM supporting tumor growth and angiogenesis, and clinically used as a therapeutic target (Tsirakis et al, 2012; Yu et al, 2003). The PDGFR inhibitor, sunitinib, is currently in a phase II trial to test its effects on MM relapse; specifically, to determine if it can inhibit growth of cancer cells by blocking enzymes related to cancer cell proliferation and blood flow to cancer (https://clinicaltrials.gov).…”

Serum soluble CD40L concentration depending on the stage of multiple myeloma and its correlation with selected angiogenic cytokines

“…17, 22 It should be emphasized that this is the first study estimating correlations between sCD40L and adhesion molecule (sVCAM-1) and growth factor (PDGF-AB) in patients with MM. It is well known that tumor growth depends on angiogenesis and lymphangiogenesis.…”