Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation

Area of Science:

• Biomedical Science
• Cancer Biology
• Cellular Communication

Background:

• Bone marrow mesenchymal stem cells (BM-MSCs) play a role in multiple myeloma (MM) pathogenesis.
• Previous studies showed mutual modulation between MM cells and BM-MSCs via translation initiation (TI) factors.
• Differences exist in the crosstalk between normal donor BM-MSCs (ND-MSCs) and MM-associated BM-MSCs (MM-MSCs).

Purpose of the Study:

• To investigate the role of soluble BM-MSC components, particularly microvesicles (MVs), in modulating MM cell phenotype and TI.
• To differentiate the effects of ND-MSCs versus MM-MSCs secretomes and their components on MM cells.
• To identify potential therapeutic targets within the BM-MSC-MM cell communication axis.

Main Methods:

• Applied ND and MM-MSC secretomes to MM cell lines (U266, ARP-1) and assessed cellular functions and TI.
• Dissected secretomes into >100kDa and <100kDa fractions to evaluate their specific effects.
• Isolated and applied MVs from ND-MSCs and MM-MSCs to MM cell lines, followed by phenotypic and TI assessments.

Main Results:

• BM-MSC secretomes (ND and MM) stimulated MM cell TI, autophagy, and proliferation.
• Secretome fractions showed differential effects: >100kDa repressed, <100kDa stimulated MM cell phenotype and TI, independent of MSC source.
• MVs from ND-MSCs inhibited MM cell proliferation, autophagy, and TI, whereas MVs from MM-MSCs stimulated these processes.

Conclusions:

• BM-MSCs, particularly through MVs, significantly influence MM cell behavior.
• ND-MSCs and MM-MSCs exert opposing effects on MM cells via their MVs.
• Understanding MV cargo is crucial for developing targeted therapies for MM by modulating the TI/proliferation/autophagy cascade.