Petrusca Daniela N, Lee Kelvin P, Galson Deborah L
Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, United States.
Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
Front Oncol. 2022 Jun 8;12:925807. doi: 10.3389/fonc.2022.925807. eCollection 2022.
Multiple myeloma (MM) is an incapacitating hematological malignancy characterized by accumulation of cancerous plasma cells in the bone marrow (BM) and production of an abnormal monoclonal protein (M-protein). The BM microenvironment has a key role in myeloma development by facilitating the growth of the aberrant plasma cells, which eventually interfere with the homeostasis of the bone cells, exacerbating osteolysis and inhibiting osteoblast differentiation. Recent recognition that metabolic reprograming has a major role in tumor growth and adaptation to specific changes in the microenvironmental niche have led to consideration of the role of sphingolipids and the enzymes that control their biosynthesis and degradation as critical mediators of cancer since these bioactive lipids have been directly linked to the control of cell growth, proliferation, and apoptosis, among other cellular functions. In this review, we present the recent progress of the research investigating the biological implications of sphingolipid metabolism alterations in the regulation of myeloma development and its progression from the pre-malignant stage and discuss the roles of sphingolipids in in MM migration and adhesion, survival and proliferation, as well as angiogenesis and invasion. We introduce the current knowledge regarding the role of sphingolipids as mediators of the immune response and drug-resistance in MM and tackle the new developments suggesting the manipulation of the sphingolipid network as a novel therapeutic direction for MM.
多发性骨髓瘤（MM）是一种使人衰弱的血液系统恶性肿瘤，其特征是癌性浆细胞在骨髓（BM）中积聚，并产生异常单克隆蛋白（M蛋白）。骨髓微环境通过促进异常浆细胞的生长在骨髓瘤发展中起关键作用，这些浆细胞最终会干扰骨细胞的稳态，加剧骨溶解并抑制成骨细胞分化。最近认识到代谢重编程在肿瘤生长以及对微环境生态位特定变化的适应中起主要作用，这使得人们开始考虑鞘脂以及控制其生物合成和降解的酶作为癌症关键介质的作用，因为这些生物活性脂质已直接与细胞生长、增殖和凋亡等细胞功能的控制相关联。在本综述中，我们介绍了研究鞘脂代谢改变在骨髓瘤发展调控及其从癌前阶段进展过程中的生物学意义的最新研究进展，并讨论了鞘脂在MM迁移和黏附、存活和增殖以及血管生成和侵袭中的作用。我们介绍了关于鞘脂作为MM免疫反应和耐药性介质作用的当前知识，并探讨了表明操纵鞘脂网络作为MM新治疗方向的新进展。
