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

Area of Science:

• Oncology
• Cell Biology
• Pharmacology

Background:

• Multiple Myeloma (MM) is treatable with chemotherapy but often relapses due to acquired drug resistance.
• Mesenchymal stromal cells (MSCs) are implicated in supporting cancer cell survival and drug resistance.
• Understanding the mechanisms of MSC-induced drug resistance is crucial for developing effective MM therapies.

Purpose of the Study:

• To investigate the role of MSCs in conferring drug resistance to Multiple Myeloma (MM) cell lines.
• To identify specific factors secreted by MSCs that mediate this drug resistance.
• To evaluate the efficacy of a novel tellurium compound, SAS, in overcoming MSC-induced drug resistance in MM.

Main Methods:

• Co-culture of MM cell lines with MSCs derived from bone marrow and adipose tissue.
• Analysis of MSC-conditioned media using mass spectrometry to identify key secreted factors.
• Treatment of MM cells with chemotherapeutic drugs and assessment of drug resistance.
• Evaluation of the effect of SAS on MM cell-MSC interaction, drug sensitivity, and signaling pathways (pAKT).

Main Results:

• MSCs, particularly bone marrow-derived MSCs, significantly induced chemoresistance in MM cell lines.
• Fibronectin was identified as a key secreted factor from MSCs mediating anti-apoptotic signals to MM cells.
• The immunomodulator tellurium compound SAS effectively blocked MM cell-fibronectin interaction and re-sensitized MM cells to chemotherapy.
• SAS treatment inhibited MSC-induced pAKT activation in MM cells, suggesting a role in overcoming resistance.

Conclusions:

• MSCs contribute to Multiple Myeloma drug resistance through secreted factors like fibronectin.
• The tellurium compound SAS demonstrates potential as a therapeutic agent to overcome MSC-mediated chemoresistance in MM.
• SAS acts by disrupting the physical interaction between MM cells and fibronectin and inhibiting downstream signaling pathways.