The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone

Curr Osteoporos Rep. 2018 Aug;16(4):443-457. doi: 10.1007/s11914-018-0453-9.

Abstract

Purpose of review: Bone marrow adipocytes have emerged in recent years as key contributors to metastatic progression in bone. In this review, we focus specifically on their role as the suppliers of lipids and discuss pro-survival pathways that are closely linked to lipid metabolism, affected by the adipocyte-tumor cell interactions, and likely impacting the ability of the tumor cell to thrive in bone marrow space and evade therapy.

Recent findings: The combined in silico, pre-clinical, and clinical evidence shows that in adipocyte-rich tissues such as bone marrow, tumor cells rely on exogenous lipids for regulation of cellular energetics and adaptation to harsh metabolic conditions of the metastatic niche. Adipocyte-supplied lipids have a potential to alter the cell's metabolic decisions by regulating glycolysis and respiration, fatty acid oxidation, lipid desaturation, and PPAR signaling. The downstream effects of lipid signaling on mitochondrial homeostasis ultimately control life vs. death decisions, providing a mechanism for gaining survival advantage and reduced sensitivity to treatment. There is a need for future research directed towards identifying the key metabolic and signaling pathways that regulate tumor dependence on exogenous lipids and consequently drive the pro-survival behavior in the bone marrow niche.

Keywords: Apoptosis; Bone marrow adipocyte; Bone metastasis; Lipids; Metabolism; Survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / secondary
  • Cell Respiration
  • Fatty Acids / metabolism
  • Glycerol / metabolism
  • Glycolysis
  • Humans
  • Lipid Metabolism*
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Oxidative Stress
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Signal Transduction
  • Tumor Hypoxia
  • Tumor Microenvironment*

Substances

  • Fatty Acids
  • Peroxisome Proliferator-Activated Receptors
  • Glycerol