Location: Children's Nutrition Research CenterTitle: Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation Author
Submitted to: Oncotarget
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2015
Publication Date: 10/7/2015
Citation: Liu, Z., Xu, J., He, J., Liu, H., Lin, P., Wan, X., Navone, N.M., Tong, Q., Kwak, L.W., Orlowski, R.Z., Yang, J. 2015. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation. Oncotarget. 6(33):34329-34341. Interpretive Summary: Multiple myeloma is a type of blood cancer. Many myeloma patients develop resistance to chemotherapy. To explore the causes of the resistance, we found that bone marrow fat cells release factors that act on myeloma cells to enhance their survival upon chemotherapy drug treatment. Therefore, fat cells and fat cell-derived factors might be new targets for reversing drug resistance and more effective myeloma treatment. Such studies shed light on the role of nutrition and diet.
Technical Abstract: A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma chemotherapy resistance. We reveal that mature human adipocytes activate autophagy and upregulate the expression of autophagic proteins, thereby suppressing chemotherapy-induced caspase cleavage and apoptosis in myeloma cells. We found that adipocytes secreted known and novel adipokines, such as leptin and adipsin. The addition of these adipokines enhanced the expression of autophagic proteins and reduced apoptosis in myeloma cells. In vivo studies further demonstrated the importance of bone marrow-derived adipocytes in the reduced response of myeloma cells to chemotherapy. Our findings suggest that adipocytes, adipocyte-secreted adipokines, and adipocyte-activated autophagy are novel targets for combatting chemotherapy resistance and enhancing treatment efficacy in myeloma patients.