Targeting SDF-1 in multiple myeloma tumor microenvironment

Cancer Lett. 2016 Sep 28;380(1):315-8. doi: 10.1016/j.canlet.2015.11.028. Epub 2015 Nov 30.

Abstract

Multiple myeloma (MM) is a type of B-cell malignancy that remains incurable to date. The bone marrow (BM) microenvironment plays a crucial role in MM progression. The chemokine SDF-1 (CXCL12) is an important actor of the BM microenvironment that has the ability to regulate numerous processes related to its malignant transformation during MM development. The activity of SDF-1 is mainly mediated by its specific receptor CXCR4, which is expressed at the surface of MM cells and various other BM cell types. Current treatments available for MM patients mainly target tumor cells but have limited effects on the BM microenvironment. In this context, SDF-1 and CXCR4 represent ideal targets for the normalization of the MM-supportive BM microenvironment. The present review focuses on the activity of SDF-1 in the MM BM microenvironment and the current efforts carried out to target the SDF-1/CXCR4 axis for treatment of MM.

Keywords: Bone marrow; CXCR4; Microenvironment; Multiple myeloma; SDF-1.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Adhesion / drug effects
  • Cell Communication / drug effects
  • Cell Movement / drug effects
  • Chemokine CXCL12 / antagonists & inhibitors*
  • Chemokine CXCL12 / metabolism
  • Humans
  • Molecular Targeted Therapy*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Neovascularization, Pathologic
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism
  • Signal Transduction / drug effects
  • Tumor Hypoxia
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4