Acting via a cell surface receptor, thyroid hormone is a growth factor for glioma cells

Faith B. Davis, Heng Yuan Tang, Ai Shih, Travis Keating, Lawrence Lansing, Aleck Hercbergs, Robert A. Fenstermaker, Ahmed Mousa, Shaker A. Mousa, Paul J. Davis, Hung Y. Lin

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)

Abstract

Recent evidence suggests that the thyroid hormone L-thyroxine (T 4) stimulates growth of cancer cells via a plasma membrane receptor on integrin αVβ3. The contribution of this recently described receptor for thyroid hormone and receptor-based stimulation of cellular mitogen-activated protein kinase [MAPK; extracellular signal-regulated kinase 1/2 (ERK1/2)] activity, to enhancement of cell proliferation by thyroid hormone was quantitated functionally and by immunologic means in three glioma cell lines exposed to T4. At concentrations of 1 to 100 nmol/L, T4 caused proliferation of C6, F98, and GL261 cells, measured by accumulation of proliferating cell nuclear antigen (PCNA) and radiolabeled thymidine incorporation. This effect was inhibited by the T 4 analogue, tetraiodothyroacetic acid, and by an α Vβ3 RGD recognition site peptide, both of which block T4 binding to integrin αVβ3 but are not agonists. Activation of MAPK by T4 was similarly inhibited by tetraiodothyroacetic acid and the RGD peptide. The thyroid hormone 3,5,3′-triiodo-L-thyronine (T3) and T4 were equipotent stimulators of PCNA accumulation in C6, F98, and GL261 cells, but physiologic concentrations of T3 are 50-fold lower than those of T4. In conclusion, our studies suggest that glioblastoma cells are thyroid hormone dependent and provide a molecular basis for recent clinical observations that induction of mild hypothyroidism may improve duration of survival in glioblastoma patients. The present experiments infer a novel cell membrane receptor-mediated basis for the growth-promoting activity of thyroid hormone in such tumors and suggest new therapeutic approaches to the treatment of patients with glioblastoma.

Original languageEnglish
Pages (from-to)7270-7275
Number of pages6
JournalCancer Research
Volume66
Issue number14
DOIs
Publication statusPublished - Jul 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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