Project ID/Number: 337-00-27/2023-05/11
Project title: Metabolic effects of bone marrow adipose tissue on multiple myeloma.
Project PI and Coordinating Institution: Drenka Trivanovic, Institute for Medical Research, University of Belgrade, Serbia (RS)
Funding Institution: Ministry of Science, Technological Development and Innovation of the Republic of Serbia
Call Information: Scientific and technological cooperation between the Republic of Serbia and the Federal Republic of Germany – 2-years Bilateral project
Fields of Science: Medicine
Consortium/Participating Institutions:
Julius-Maximilians-Universität Würzburg, Germany
Institute for Orthopedy Banjica, Belgrade, Serbia
Grant Duration: 2023-2024
Budget: 4.000,00 € Serbian side (+7.500,00 € German side)
Project Abstract:
Multiple myeloma (MM) is the second most‐prevalent hematologic malignancy and incurable clonal disease of the plasma cell that grows within the bone marrow (BM) causing destructive bone lesions in patients. As a disease of elderly, MM is associated with increased bone marrow adipose tissue (BMAT) which can occupy 70% of the BM volume wherein MM originates and resides. There are strong indications that BMAT may provide a supportive microenvironment of MM cells to grow, survive, and become drug resistant and this complex communication is a topic of intense investigation. However, the most published results on this topic are based on human BM mesenchymal stromal cell (MSC)-derived adipocytes, but it is becoming clear that differentiated MSC cannot fully recapitulate the physiology of BM adipocytes (BMAd). In general, cancer-associated adipocytes support tumor cells through various mechanisms i) synergistic metabolic reprogramming of cancer cells; ii) secretion of adipokines and iii) modulation of tumor microenvironment through immunosuppression and regulation of metabolic demands, triggering alternative metabolic pathways, including glycolysis and fatty acid oxidation (FAO). Since adipocytes have been shown to support cancer cell growth and survival by influencing cell mitochondrial activity and lipid metabolism, we hypothesized that BMAd population represent one of the key regulators of MM persistence in BM controlling FAO in MM cells. Although not fully understood, FAO may play an essential role in MM metabolism with or without concurrent aerobic glycolysis. Indeed, a metabolic shift from aerobic glycolysis towards more FAO has been reported to increase leukemic cell survival. Thus, exploiting the energy-producing metabolic pathways mediated by BMAT within clonal plasma cells for diagnostic and therapeutic purposes in MM should be explored in the future. Realization of this project, resulting from the mutual work of German and Serbian team, will bring novel BMAT-plasma/MM cell co-culture systems established for better understanding of the role of BMAT in MM pathology and identification of specific metabolic regulators of clinical interests.
Contact for Collaborations: drenka.trivanovic@imi.bg.ac.rs