IRE1a-Induced FilaminA Phosphorylation Enhances Migration of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients

Abstract

Multiple myeloma (MM) is an aggressive malignancy that shapes, during its progression, a pro-tumor microenvironment characterized by altered protein secretion and the gene expression of mesenchymal stem cells (MSCs). In turn, MSCs from MM patients can exert an high pro-tumor activity and play a strong immunosuppressive role. Here, we show, for the first time, greater cell mobility paralleled by the activation of FilaminA (FLNA) in MM-derived MSCs, when compared to healthy donor (HD)-derived MSCs. Moreover, we suggest the possible involvement of the IRE1a-FLNA axis in the control of the MSC migration process. In this way, IRE1a can be considered as a good target candidate for MM therapy, considering its pro-survival, pro-osteoclast and chemoresistance role in the MM microenvironment. Our results suggest that IRE1a downregulation could also interfere with the response of MSCs to MM stimuli, possibly preventing cell–cell adhesion-mediated drug resistance. In addition, further investigations harnessing IRE1a-FLNA interaction could improve the homing efficiency of MSC as cell product for advanced therapy applications.

Ex vivo expansion in a clinical grade medium, containing growth factors from human platelets, enhances migration capacity of adipose stem cells

“…As above mentioned, expression of these two proteins is mandatory for cell migration, but they both appear to be not involved in the SRGF mediated increase of ASC migration potential. We previously showed that levels of phosphorylated FLNA are increased in highly migrating cells, as MSC derived from multiple myeloma patients ( 17 ). In present results, phoshorilated FLNA levels were not affected by SRGF or FBS addition to the cell culture medium or by the migration stimulus.…”

“…Previous publications showed α-smooth muscle actin (αSMA) is required for cell diapedesis ( 15 ), even though it was also shown to inhibit migration of selected primary cells ( 16 ). We previously showed ( 17 ) that FilaminA (FLNA) is increased in fast migrating cells, as MSC derived from the bone marrow of multiple myeloma patients. In this work, we aimed to investigate the impact of SRGF on the migration potential of expanded ASC.…”