IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13

Neoplasia. Sep-Oct 2002;4(5):388-99. doi: 10.1038/sj.neo.7900234.

Abstract

We have found that binding sites for interleukin-13 (IL-13) are overexpressed in a vast majority of high-grade astrocytomas (HGAs). These binding sites for IL-13 are distinct from the physiological receptor in that it does not bind IL-4. We also demonstrated that IL-13 receptor alpha 2 protein chain (IL-13Ralpha2), an IL-4-independent receptor for IL-13, is abundant among HGAs, but not in normal organs. To examine if IL-13Ralpha2 is the tumor-associated site for IL-13, we stably transfected normal Chinese hamster ovary (CHO) cells and glioma G-26 cells to express either human (h) or murine (m) IL-13Ralpha2. CHO-hIL-13Ralpha2(+) cells and G-26-h/mIL-13Ralpha2(+) cells, and not CHO and G-26 parental or mock-transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL-13Ralpha2(+) cells also became highly susceptible to the killing by an IL-13-based cytotoxic fusion protein. In loss of function studies, a HGA cell line, SNB-19, was transfected with antisense (as) hIL-13Ralpha2. as-SNB-19-hIL-13Ralpha2(+) cells lost their natural affinity towards IL-13 and became resistant to IL-13-based cytotoxins. The fact, that IL-13Ralpha2-positive cells bind IL-13 independent of IL-4, become susceptible to IL-13 cytotoxins, and cells deprived of IL-13Ralpha2 receptor lose these features, demonstrates that IL-13Ralpha2 is the brain tumor-associated receptor for IL-13.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Northern
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • CHO Cells / metabolism
  • Cricetinae
  • DNA Primers / chemistry
  • DNA, Antisense / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Interleukin-13 / metabolism*
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / metabolism
  • Polymerase Chain Reaction
  • Protein Binding
  • RNA / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-13
  • Transfection
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • DNA, Antisense
  • IL13RA1 protein, human
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Interleukin-4
  • RNA