This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davis, F. B. Articles by Lin, H.-Y. Search for Related Content PubMed PubMed Citation Articles by Davis, F. B. Articles by Lin, H.-Y.

Acting via a Cell Surface Receptor, Thyroid Hormone Is a Growth Factor for Glioma Cells

¹ Ordway Research Institute, Inc.; ² Research Service, Stratton Veterans Affairs Medical Center; ³ Albany College of Pharmacy; ⁴ Wadsworth Center, New York State Department of Health, Albany, New York; ⁵ Department of Radiation Oncology, The Cleveland Clinic, Cleveland, Ohio; and ⁶ Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Faith B. Davis, Ordway Research Institute, Inc., 150 New Scotland Avenue, Albany, NY 12208. Phone: 518-641-6465; Fax: 518-641-6303; E-mail: fdavis{at}ordwayresearch.org.

Recent evidence suggests that the thyroid hormone L-thyroxine (T₄) stimulates growth of cancer cells via a plasma membrane receptor on integrin _Vß₃. 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 T₄ analogue, tetraiodothyroacetic acid, and by an _Vß₃ RGD recognition site peptide, both of which block T₄ binding to integrin _Vß₃ 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. (Cancer Res 2006; 66(14): 7270-5)

This article has been cited by other articles:

				A Scarlett, M P Parsons, P L Hanson, K K Sidhu, T P Milligan, and J M Burrin Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin {alpha}V{beta}3 J. Endocrinol., March 1, 2008; 196(3): 509 - 517. [Abstract] [Full Text] [PDF]

				A. H. Conrad, J. M. Strafuss, M. D. Wittman, S. Conway, and G. W. Conrad Thyroxine Increases the Rate but Does Not Alter the Pattern of Innervation during Embryonic Chick Corneal Development Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 139 - 153. [Abstract] [Full Text] [PDF]

				I. Irrcher, D. R. Walkinshaw, T. E. Sheehan, and D. A. Hood Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo J Appl Physiol, January 1, 2008; 104(1): 178 - 185. [Abstract] [Full Text] [PDF]

				H.-Y. Lin, H.-Y. Tang, T. Keating, Y.-H. Wu, A. Shih, D. Hammond, M. Sun, A. Hercbergs, F. B. Davis, and P. J. Davis Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated Carcinogenesis, January 1, 2008; 29(1): 62 - 69. [Abstract] [Full Text] [PDF]

				S. R. Hammes and E. R. Levin Extranuclear Steroid Receptors: Nature and Actions Endocr. Rev., December 1, 2007; 28(7): 726 - 741. [Abstract] [Full Text] [PDF]

				A. Hercbergs and P. Davis Hypothyroidism in the Patient With Cancer: How Much Thyroid Supplementation Is "Safe"? Arch Otolaryngol Head Neck Surg, June 1, 2007; 133(6): 625 - 626. [Full Text] [PDF]