ECTS2016 Poster Presentations Cancer and bone: basic, translational and clinical (37 abstracts)
Contribution of multiple myeloma-derived exosomes to bone disease
Lavinia Raimondi 1 , Angela De Luca 1 , Valeria Carina 1 , Valentina Agnese 1 , Simona Fontana 2 , Francesca Monteleone 2 , Laura Saieva 2 , Riccardo Alessandro 2 & Gianluca Giavaresi 1,
1Rizzoli Orthopedic Institute, Palermo, Italy; 2University of Palermo, Palermo, Italy; 3Rizzoli Orthopedic Institute, Bologna, Italy.
Bone disease is the most frequent complication in multiple myeloma (MM) resulting in pain, bone fractures, spinal cord compression and hypercalcemia. Within the bone marrow microenvironment (BMM), MM cells interact with bone cells to enhance bone resorption activity and compromise new bone formation mechanism; in turn, BMM provides a survival and drug resistance framework by interaction of MM cells with bone marrow components. Exosomes are important mediators of crosstalk between MM cells and BMM, as new evidence indicates that exosomes secreted by MM cells positively modulate osteoclast differentiation, playing a key role in destructive osteolytic processes. Here, we proposed that MM cell-derived exosomes contribute to Osteoblast/Osteoclast uncoupling in osteolytic lesions, playing a critical role in the regulation of RANK/RANK-L pathway inside the BMM. Moreover, we aimed to investigate effect of osteoclasts differentiated after treatment with MM-cell derived exosomes (OCs MM-exo treated) on survival and apoptosis of MM cells, by better understanding the intricate networks among molecules which control these processes.
MM cell lines cultured with a conditioned medium obtained by OCs MM-exo treated, showed increased expression of pro-survival and anti-apoptotic factors; of note, MM cells produced much more RANK-L and DKK1 factors, critical regulators of bone remodelling processes, compared to untreated cells. Proteomic analysis of exosomes isolated from MM cells revealed the presence of extracellular matrix proteins, as well as factors correlated with bone remodelling mechanisms. Luminex multiplex cytokine analysis highlighted presence of proteins of uPA system, involved in important biological events such as cancer cell invasion, adhesion and bone matrix degradation. In conclusion, our results show that MM-exosomes affect cancer cell survival, and anti-apoptosis mechanisms, sustaining therefore MM bone disease. Finally, further studies on the molecular content of exosomes will greatly improve the understanding of the nanovesicles role on the onset and severity of osteolytic lesions in MM.
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Bone Abstracts
ISSN 2052-1219 (online)
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