Tellurium compound provides pro-apoptotic signaling in drug resistant multiple myeloma

Abstract

Multiple Myeloma, effectively treated by chemotherapeutic drugs, relapses due to drug resistance. We tested here the capacity of mesenchymal stromal cells, from the bone marrow of patients or from adipose tissue of healthy individuals, to induce drug resistance in Myeloma cell lines. We show that drug resistance can be achieved by factors secreted by the various MSC's. Mass spectrometry analysis of MSC's conditioned media revealed that fibronectin, was particularly instrumental in providing anti-apoptotic signals to MM cells. Moreover, we demonstrate that SAS ([octa-O-bis-(R,R)tartarate ditellurane]), an immunomodulator Tellurium compound, is not only able of blocking the physical interaction between MM cells and fibronectin but is also capable of re-sensitizing the cells to the chemotherapeutic drugs. Finally, we show that this re-sensitization is coupled with the blocking of pAKT induction, in MM cells, by the MSC's. These results indicate that SAS may be useful in the treatment of drug resistant MM.

Keywords: Multiple myeloma; drug resistance; fibronectin; mesenchymal stromal cells; tellurium.