Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy

Leuk Res. 2013 May;37(5):503-9. doi: 10.1016/j.leukres.2012.12.013. Epub 2013 Jan 17.

Abstract

Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1α. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse.

Publication types

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

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Chemokine CXCL12 / metabolism
  • Daunorubicin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Transplantation, Isogeneic
  • Tumor Microenvironment / drug effects*
  • Vincristine / pharmacology*

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Vincristine
  • Daunorubicin