Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells

Cancer Lett. 2014 Jun 28;348(1-2):71-6. doi: 10.1016/j.canlet.2014.03.009. Epub 2014 Mar 18.

Abstract

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demonstrated that exosomes released from CML cells stimulate bone marrow stromal cells to produce IL 8 that, in turn, is able to modulate both in vitro and in vivo the leukemia cell malignant phenotype.

Keywords: Bone marrow stromal cells; Chronic myelogenous leukemia; Exosomes; Interleukin 8; Tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Exosomes / metabolism*
  • Heterografts
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Paracrine Communication*
  • Phenotype
  • Signal Transduction
  • Stem Cell Niche
  • Tumor Microenvironment
  • Up-Regulation

Substances

  • CXCL8 protein, human
  • Interleukin-8