title: Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases.
abstract: Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield, Rm 6304, Detroit, MI, 48201, USA.
authors.forename: Aimalie L
authors.initials: AL
authors.lastname: Hardaway
authors.forename: Mackenzie K
authors.initials: MK
authors.lastname: Herroon
authors.forename: Erandi
authors.initials: E
authors.lastname: Rajagurubandara
authors.forename: Izabela
authors.initials: I
authors.lastname: Podgorski
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents