High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma

Cancer Lett. 2007 Oct 28;256(2):196-206. doi: 10.1016/j.canlet.2007.06.001. Epub 2007 Jul 10.

Abstract

We surveyed IL-21 receptor (IL-21R) in leukemia and lymphoma and found that follicular lymphoma cells showed exceptionally high IL-21R expression. Notably, IL-21 showed divergent effects depending on the cell origin: growth stimulation in Burkitt lymphoma cell lines and adult T cell leukemia/lymphoma cell lines but induction of apoptosis in B lymphoma cell lines with t(14;18)(q32;q21), a marker karyotype of follicular lymphoma. IL-21 activated caspase-8 and -3 and reduced mitochondrial membrane potential. More importantly, IL-21 decreased Bcl-2 expression but increased Bax expression. These results support a new therapeutic approach using the IL-21/IL-21R system in follicular lymphoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis* / drug effects
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Humans
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Interleukins / therapeutic use
  • Jurkat Cells
  • K562 Cells
  • Leukemia / drug therapy
  • Leukemia / enzymology
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / enzymology
  • Lymphoma, Follicular / metabolism*
  • Lymphoma, Follicular / pathology
  • Membrane Potential, Mitochondrial
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Interleukin-21 / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction* / drug effects
  • Time Factors
  • Tumor Cells, Cultured
  • U937 Cells
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Interleukins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-21
  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • Caspase 3
  • Caspase 8
  • interleukin-21