Tumor microenvironment affects exogenous sodium/iodide symporter expression

Fabio Castillo-Rivera, Alejandro Ondo-Méndez, Julien Guglielmi, Jean Marie Guigonis, Lun Jing, Sabine Lindenthal, Andrea Gonzalez, Diana López, Béatrice Cambien, Thierry Pourcher

Research output: Contribution to journalArticlepeer-review

9 Scopus citations
27 Downloads (Pure)

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-localization. Modifications in the expression of proteins and metabolites involved in plasma membrane localization and in energy metabolism were found using untargeted proteomics and metabolomics approaches. In conclusion, our results provide evidence that hypoxia and quiescence impair NIS expression at the plasma membrane, and iodide uptake. Our study also shows that the tumor microenvironment is an important parameter for successful NIS-based cancer treatment.

Original languageEnglish (US)
Article number100937
JournalTranslational Oncology
Volume14
Issue number1
DOIs
StatePublished - Jan 30 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Tumor microenvironment affects exogenous sodium/iodide symporter expression'. Together they form a unique fingerprint.
  • VI SIMPOSIO LATINOAMERICANO DE GASTROENTEROLOGÍA ONCOLÓGICA

    Alejandro Oyono Ondo Mendez (Participant), Fabio Castillo Rivera (Participant), Ruth Garzón Fernández (Participant), Martha Leonor Pinzon Daza (Participant), Lilia Del Riesgo Prendes (Participant) & Thierry Pourcher (Participant)

    Apr 5 2017Apr 8 2017

    Activity: Participation or organization of an eventParticipation in conference

  • EMBO Conference Series: Cellular signalling and cancer therapy

    Lorena Xiomara Gonzalez (Participant), Daniel Fernando López (Participant), Fabio Castillo Rivera (Participant), Martha Leonor Pinzon Daza (Participant), Lilia Del Riesgo Prendes (Participant), Thierry Pourcher (Participant), Ruth Elizabeth Garzon Fernandez (Participant) & Alejandro Oyono Ondo Mendez (Participant)

    May 27 2016

    Activity: Participation or organization of an eventParticipation in conference

  • 2nd Annual Meeting of the International Society of Cancer Metabolism

    Fabio Castillo Rivera (Participant), Andrés Romero (Participant), Alejandro Oyono Ondo Mendez (Participant), Ximena Muñoz (Participant), Lorena Xiomara Gonzalez (Participant), Daniel Fernando López (Participant), Thierry Pourcher (Participant), Lilia Del Riesgo Prendes (Participant), Martha Leonor Pinzon Daza (Participant), Luisa Marina Matheus Merino (Participant) & Ruth Elizabeth Garzon Fernandez (Participant)

    Sep 16 2015

    Activity: Participation or organization of an eventParticipation in conference

Cite this