Tumor microenvironment affects exogenous sodium/iodide symporter expression

Translational Oncology
Fabio Castillo-RiveraThierry Pourcher

Abstract

For decades, sodium/iodide symporter NIS-mediated iodide uptake has played a crucial role in the radioactive ablation of thyroid cancer cells. NIS-based gene therapy has also become a promising tool for the treatment of tumors of extrathyroidal origin. But its applicability has been hampered by reduced expression of NIS, resulting in a moderated capacity to accumulate 131I and in inefficient ablation. Despite numerous preclinical enhancement strategies, the understanding of NIS expression within tumors remains limited. This study aims at a better understanding of the functional behavior of exogenous NIS expression in the context of malignant solid tumors that are characterized by rapid growth with an insufficient vasculature, leading to hypoxia and quiescence. Using subcutaneous HT29NIS and K7M2NIS tumors, we show that NIS-mediated uptake and NIS expression at the plasma membrane of cancer cells are impaired in the intratumoral regions. For a better understanding of the underlying molecular mechanisms induced by hypoxia and quiescence (separately and in combination), we performed experiments on HT29NIS cancer cells. Hypoxia and quiescence were both found to impair NIS-mediated uptake through mechanisms including NIS mis-localiz...Continue Reading

References

Sep 13, 1996·Biochemical and Biophysical Research Communications·P A SmanikS M Jhiang
Oct 1, 1996·Thyroid : Official Journal of the American Thyroid Association·J G KiangR C Smallridge
Feb 22, 2001·European Journal of Endocrinology·P H EngL E Braverman
Apr 6, 2001·The Journal of Biological Chemistry·C RiedelN Carrasco
Nov 13, 2001·Gene Therapy·C SpitzwegJ C Morris
Feb 13, 2002·Thyroid : Official Journal of the American Thyroid Association·Anne BolandMichel Perricaudet
Mar 22, 2003·Blood·David DingliStephen J Russell
Nov 25, 2003·Journal of Cellular Biochemistry·David DingliJohn C Morris
Aug 18, 2005·The Journal of Clinical Endocrinology and Metabolism·Zhaoxia ZhangSissy M Jhiang
Feb 21, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thorsten PetrichEyck Pötter
Mar 3, 2006·PLoS Biology·Hilary A CollerJames M Roberts
Jun 9, 2007·The Journal of Clinical Investigation·Claire MagnonMartin Schlumberger
Jul 20, 2007·Endocrine-related Cancer·Douangsone D VadysirisackSissy M Jhiang
Aug 21, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kwang Il KimMyung Chul Lee
Oct 5, 2007·The Journal of Biological Chemistry·Douangsone D VadysirisackSissy M Jhiang
Apr 12, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Michael J WillhauckChristine Spitzweg
Aug 21, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kenneth N BartonBenjamin Movsas
Aug 27, 2009·Journal of Cell Science·Vicki E SmithChristopher J McCabe
Oct 29, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Inge PeerlinckGeorges Vassaux
Jul 1, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mohan HingoraniKevin J Harrington
Aug 10, 2011·Nature Reviews. Endocrinology·Christoph ReinersFrederik A Verburg
Jan 24, 2012·Current Gene Therapy·Alan R PenheiterStephanie K Carlson
Apr 14, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan McIntyreAdrian L Harris
Aug 31, 2013·Biochimica Et Biophysica Acta·Elisabeth DarrouzetThierry Pourcher
Dec 7, 2013·Endocrine Reviews·Carla PortulanoNancy Carrasco
Sep 23, 2014·Hormones & Cancer·Aparna LakshmananSissy M Jhiang
Feb 11, 2015·Biomaterials·Peggy Richard-FiardoGeorges Vassaux
Jul 2, 2015·Journal of Proteome Research·Yanan XuShankai Yin

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Methods Mentioned

BETA
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xenografts
transfection
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