Tucci Marco, Stucci Stefania, Felici Claudia, Cafforio Paola, Resta Leonardo, Rossi Roberta, Silvestris Franco
Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy.
Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Bari, Italy.
Br J Haematol. 2016 Apr;173(1):59-69. doi: 10.1111/bjh.13922. Epub 2016 Jan 5.
Cilengitide (CLG) is an inhibitor of both αv β3 and αv β5 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 αv β3 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 αv β3 and αv β5 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.
西仑吉肽（CLG）是αvβ3和αvβ5整合素的抑制剂，对胶质母细胞瘤具有明确的抗肿瘤作用。临床前研究表明其具有抑制转移性亲骨性肿瘤骨吸收特性的能力，并且我们之前已经表明，多发性骨髓瘤（MM）浆细胞中αvβ3的失活会导致其在骨基质上的体外破骨细胞（OC）样活性耗竭。在此，我们研究了CLG对MM细胞这一功能特性的影响。检测了19例患者原代骨髓MM细胞上的αvβ3和αvβ5，并与MM细胞系及健康供体的OCs平行研究了CLG对增殖、凋亡和黏附的影响。此外，针对整合素分子途径的细胞内激酶激活情况，探讨了CLG对恶性浆细胞在磷酸钙上产生侵蚀性腔隙能力的影响。利用超微结构显微镜评估了CLG对细胞黏附作用影响下MM细胞的形态变化。我们的研究数据表明，CLG通过破坏MM细胞的黏附特性来抑制其骨吸收功能。亲骨性肿瘤临床前研究有必要进行进一步调查。
