Emerging roles of endoglin/CD105 and angiogenic cytokines for disease development and progression in multiple myeloma patients

Abstract

Angiogenesis is an essential process for the expansion of multiple myeloma (MM), in which many angiogenic factors participate. Endoglin (CD105) is a transforming growth factor-β co-receptor, being mainly expressed in angiogenic endothelial cells and has been used as a marker of tumor angiogenesis, having prognostic potential. The aim of the study was to evaluate serum levels of soluble CD105 (sCD105) in MM patients, both during diagnosis and after effective conventional chemotherapy, in the plateau phase, and to correlate them with the clinical stage of the disease, as well as with the known angiogenic factors vascular endothelial growth factor, angiogenin and interleukin-18 (IL-18). Serum levels of the aforementioned factors were measured, by enzyme-linked immunosorbent assay, in 56 newly diagnosed MM patients, in 35 of them who entered plateau phase and in 24 healthy controls. Bone marrow aspirations were also performed in all patients to determine plasma cell infiltration. All measured cytokines were higher in MM patients compared with controls and with advancing disease stage (p < 0.001 for all cases). Furthermore, the values of all factors decreased significantly in the plateau phase (p < 0.001 for all cases). Serum levels of sCD105 correlated with the other angiogenic cytokines, whereas only serum levels of angiogenin had prognostic value for the survival. In conclusion, CD105 and the angiogenic cytokines vascular endothelial growth factor, angiogenin and IL-18, seem to have emerging roles both in angiogenesis and tumor growth in MM.

The role of bone morphogenetic proteins in myeloma cell survival

“…[39] Both myeloma cell lines and primary cells were shown to express TGF-β mRNA and active protein, [40,41] however it was also reported that myeloma cells do not produce active TGF- Expression of the other type 3 receptor, endoglin, is induced by TGF-β and hypoxia, [44,45] and increased levels of soluble endoglin in myeloma patients were associated with advanced disease and tumor growth. [46,47] Membrane-bound endoglin is found on some myeloma cell lines, but lack on others. [35] Expression of selected receptors and their putative ligands in myeloma cells is summarized in Table 1.…”

Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

“…31, 32, 33 It was reported that serum levels of endoglin were higher in multiple myeloma patients than in healthy controls and that high levels were associated with advanced disease, tumor growth and angiogenesis. 34, 35 …”

Alterations in Hoffa’s fat pad induced by an inflammatory response following idealized anterior cruciate ligament surgery

“…Following ACL-R surgery, the biological events within the knee joint tissue are similar to those observed during wound healing. Recent studies have shown that endoglin (CD105) is a TGFb co-receptor and marker of tumor angiogenesis [39]. Angiogenesis is also essential for repair processes and the increased fibrosis observed in the IPFP tissue following ACL-R surgery could be partially attributed to the interplay of these two biologically relevant molecules.…”