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Cilengitide restrains the osteoclast-like bone resorbing activity of myeloma plasma cells
Marco Tucci1, Stefania Stucci1, Claudia Felici1
1Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy.
Abstract:
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.
Insights
Cilengitide (CLG) inhibits αv β3 and αv β5 integrins, reducing multiple myeloma (MM) cell bone resorption. This study shows CLG disables MM cell adhesion, a key mechanism for its anti-tumour effects.
Area of Science:
- Oncology
- Integrin Biology
- Bone Metastasis Research
Background:
- Cilengitide (CLG) targets αv β3 and αv β5 integrins, showing anti-tumour effects in glioblastoma.
- Previous research indicated αv β3 integrin blockade exhausts multiple myeloma (MM) plasma cell osteoclast-like activity.
- The role of CLG in modulating MM cell bone resorption requires further investigation.
Purpose of the Study:
- To investigate the effect of Cilengitide (CLG) on the bone resorbing function of multiple myeloma (MM) cells.
- To evaluate the impact of CLG on MM cell proliferation, apoptosis, adhesion, and erosive lacunae formation.
- To explore the relationship between CLG's effects and the activation of intracellular kinases in MM cells.
Main Methods:
- Quantification of αv β3 and αv β5 integrins on primary MM cells from 19 patients.
- Assessment of CLG's effects on MM cell proliferation, apoptosis, and adhesion using cell lines and OCs from healthy donors.
- Exploration of CLG's impact on malignant plasma cell erosive capacity and associated kinase activation, utilizing ultrastructural microscopy.
Main Results:
- Cilengitide (CLG) was confirmed to inhibit αv β3 and αv β5 integrins on MM cells.
- CLG demonstrated a capacity to restrain the bone resorbing function of MM cells.
- The mechanism involves the disabling of MM cell adhesion properties, impacting their interaction with bone substrate.
Conclusions:
- Cilengitide (CLG) effectively restrains the bone resorbing function of multiple myeloma (MM) cells.
- Disabling MM cell adhesion properties is a key mechanism by which CLG exerts its effects.
- Further pre-clinical studies of CLG in osteotropic tumours are warranted to explore its therapeutic potential.
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