Tumor microenvironment affects exogenous sodium/iodide symporter expression
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 redu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523320304290 |
| _version_ | 1818644727904337920 |
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| author | Fabio Castillo-Rivera Alejandro Ondo-Méndez Julien Guglielmi Jean-Marie Guigonis Lun Jing Sabine Lindenthal Andrea Gonzalez Diana López Béatrice Cambien Thierry Pourcher |
| author_facet | Fabio Castillo-Rivera Alejandro Ondo-Méndez Julien Guglielmi Jean-Marie Guigonis Lun Jing Sabine Lindenthal Andrea Gonzalez Diana López Béatrice Cambien Thierry Pourcher |
| author_sort | Fabio Castillo-Rivera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T00:19:27Z |
| format | Article |
| id | doaj.art-d5baa942ad04456ab8599c560d83ff6e |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-17T00:19:27Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-d5baa942ad04456ab8599c560d83ff6e2022-12-21T22:10:37ZengElsevierTranslational Oncology1936-52332021-01-01141100937Tumor microenvironment affects exogenous sodium/iodide symporter expressionFabio Castillo-Rivera0Alejandro Ondo-Méndez1Julien Guglielmi2Jean-Marie Guigonis3Lun Jing4Sabine Lindenthal5Andrea Gonzalez6Diana López7Béatrice Cambien8Thierry Pourcher9Clinical Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogota DC, ColombiaClinical Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogota DC, ColombiaTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, FranceTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, FranceTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, FranceTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, FranceCentro de Bioinformática y Biología Computacional de Colombia-BIOS, Manizales, ColombiaCentro de Bioinformática y Biología Computacional de Colombia-BIOS, Manizales, Colombia; Department of Biological Science, Faculty of Agricultural Sciences, Universidad Nacional de Colombia, Sede Palmira, Palmira, ColombiaTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, FranceTransporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, 06107 Nice, France; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1936523320304290Sodium/Iodide symporter (NIS)Tumor microenvironmentQuiescenceHypoxiaProtein trafficking |
| spellingShingle | Fabio Castillo-Rivera Alejandro Ondo-Méndez Julien Guglielmi Jean-Marie Guigonis Lun Jing Sabine Lindenthal Andrea Gonzalez Diana López Béatrice Cambien Thierry Pourcher Tumor microenvironment affects exogenous sodium/iodide symporter expression Translational Oncology Sodium/Iodide symporter (NIS) Tumor microenvironment Quiescence Hypoxia Protein trafficking |
| title | Tumor microenvironment affects exogenous sodium/iodide symporter expression |
| title_full | Tumor microenvironment affects exogenous sodium/iodide symporter expression |
| title_fullStr | Tumor microenvironment affects exogenous sodium/iodide symporter expression |
| title_full_unstemmed | Tumor microenvironment affects exogenous sodium/iodide symporter expression |
| title_short | Tumor microenvironment affects exogenous sodium/iodide symporter expression |
| title_sort | tumor microenvironment affects exogenous sodium iodide symporter expression |
| topic | Sodium/Iodide symporter (NIS) Tumor microenvironment Quiescence Hypoxia Protein trafficking |
| url | http://www.sciencedirect.com/science/article/pii/S1936523320304290 |
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