Signaling interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

Abstract

In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as:self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms,tissue invasion and metastasis, limitless replicative potential, and sustainedangiogenesis. Eleven years later, two new Hallmarks were added to the list (avoidingimmune destruction and reprograming energy metabolism) and two new tumor characteristics(tumor-promoting inflammation and genome instability and mutation) (2).In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantlyin the bone marrow (BM), it is clear that all these hallmarks and characteristicsare in play, contributing to tumor initiation, drug resistance, disease progression, andrelapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MMoncogenesis and disease progression, potentially affecting MM cell metabolism, immuneaction, inflammation, and influences on angiogenesis. In this review, we discuss theconfirmed and hypothetical contributions of BMAT to MM development and diseaseprogression. BMAT has been understudied due to technical challenges and a previouslack of appreciation for the endocrine function of this tissue. In this review, we define thedynamic, responsive, metabolically active BM adipocyte. We then describe how BMATinfluences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrinesignaling, and bone disease. We then discuss the connection between BMAT andsystemic inflammation and potential treatments to inhibit the feedback loops betweenBM adipocytes and MM cells that support MM progression. We aim for researchers touse this review to guide and help prioritize their experiments to develop better treatmentsor a cure for cancers, such as MM, that associate with and may depend on BMAT.