Reduced elastin in multiple myeloma niche promotes cell proliferation

Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interactions with the microenvironment promote disease progression and drug resistance. Previously, we have shown that bone marrow mesenchymal stem cells (BM-MSCs) (MM and normal donors- ND) derived extracellular matrix (ECM) affected MM cell lines differentially with a pro-MM effect attributed to MM-MSCs' ECM. Here we studied the composition of BM-MSC's ECM (ND versus MM) with focus on elastin (ELN). Isolated BM-MSCs' ECM mass spectrometry (proteomics) demonstrated distinct differences in proteins repertoire in a source dependent manner (MM or ND-MSCs) with ELN being the most significantly decreased protein in MM-MSCs ECM. To study this observation, we cultured MM cell lines (MM1S, RPMI-8226) and BM-MSCs with/without ELN and assayed the cells' phenotype. We demonstrated that supplementing ELN to MM cell lines reduced live cell counts and increased cell adhesion. ELN also decreased MM-MSCs' proliferation but did not affect ND-MSCs. Importantly, ELN addition to MM-MSC ECM abrogated its pro-MM effect on MM cells' proliferation. These novel findings underscore a suppressive role for ELN in MM and suggest it may hold potential diagnostic and therapeutic purposes.