Bone disease is the most frequent complication in multiple myeloma (MM). In MM bone disease the perfect balance between osteoclasts (OCs) and osteoblasts (OBs) activity is completely abrogated in favour of OCs, thus resulting in osteolysis. Exosomes are nanovesicles, released from cancer cells that actively transfer information (proteins, microRNAs and mRNAs) to target cells, thus influencing their behaviour and strongly modifying the tumor microenvironment as well as the premetastatic niche. In MM, cell-derived exosomes are considered mediators for myeloma angiogenesis,while MM Bone Marrow-derived exosomes significantly act on survival, migration and drug resistance of MM cells. Our laboratory have recently demonstrated that MM exosomes may modulate osteoclastogenesis,although the molecular components involved in this process remained elusive as well as the possible role of MM exosomes in the inhibition of bone formation.
The aims of our research are to:- investigate the molecular components in MM exosomes driving osteoclastogenesis through -omic technologies and functional assays;- investigate if MM exosomes are able to influence also osteoblast activityMurine Raw264.7 cells, human pre-osteoclast cells and human mesenchymal stem cells will be stimulated with normoxic, hypoxic exosomes as well as with patient derived MM exosomes and normal controls. Exosomes deprived of amphiregulin will be used to investigate the role of this molecule as driver of osteoclastogenesis. Quantitative Real Time Pcr, as well as western blot and Elisa Assays will be used to determine expression of differentiation markers for both OCs and OBs. Proteomic analyses with LQ Orbitrap will be also used to characterize exosome protein content under normoxic and hypoxic conditions. Exosomes isolated from plasma of patients affected by MM and from controls will be also used.
|Data di inizio/fine effettiva||1/2/17 → 1/1/20|