Cilengitide restrains the osteoclast‐like bone resorbing activity of myeloma plasma cells

• Published in: British journal of haematology 2016-04, Vol.173 (1), p.59-69
• Main Authors: Tucci, Marco, Stucci, Stefania, Felici, Claudia, Cafforio, Paola, Resta, Leonardo, Rossi, Roberta, Silvestris, Franco
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; bone disease; Bone Resorption - metabolism; Bone Resorption - pathology; Cell Adhesion - drug effects; Cell Proliferation - drug effects; cilengitide; Female; Humans; Integrin alphaVbeta3 - metabolism; Male; multiple myeloma; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Neoplasm Proteins - metabolism; osteoclasts; Osteoclasts - metabolism; Osteoclasts - pathology; Plasma Cells - metabolism; Plasma Cells - pathology; Receptors, Vitronectin - metabolism; Snake Venoms - pharmacology; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.13922

Summary Cilengitide (CLG) is an inhibitor of both αvβ3 and αvβ5 integrins, with a defined anti‐tumour effect in glioblastoma. Pre‐clinical studies demonstrate its ability to restrain the bone resorbing property of metastatic osteotropic tumours and we have previously shown that the disablement of αvβ3 in multiple myeloma (MM) plasma cells results in exhaustion of their in vitro osteoclast (OC)‐like activity on bone substrate. Here, we investigated the effect of CLG on this functional property of MM cells. Both αvβ3 and αvβ5 were measured on primary marrow MM cells from 19 patients, and the effect of CLG on proliferation, apoptosis and adhesion was investigated in parallel with MM cell lines and OCs from healthy donors. In addition, the effect of CLG on the capability of malignant plasma cells to produce erosive lacunae on calcium phosphate was explored in relation to the activation of intracellular kinases of molecular pathways of both integrins. Ultrastructural microscopy was used to evaluate the morphological changes in MM cells due to the effect of CLG on cell adhesion. The data from our study demonstrate that CLG restrains the bone resorbing function of MM cells by disabling their adhesion properties. Further investigations in pre‐clinical studies of osteotropic tumours are warranted.