In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer
Abstract. Background. Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer. Methods. By transfection of a 5 hypoxia-responsiv...
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doaj-c40bff9de1df4a8e88dae288c1f4fd6c2020-12-02T07:55:06ZengWolters KluwerChinese Medical Journal0366-69992542-56412020-01-01133220521110.1097/CM9.0000000000000616202001200-00011In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancerHe-Wen TangHai-Liang FengMing WangQing-Li ZhuYu-Qin LiuYu-Xin JiangYi CuiAbstract. Background. Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer. Methods. By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hre-gfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD). Results. In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD. Conclusions. The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.http://journals.lww.com/10.1097/CM9.0000000000000616 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
He-Wen Tang Hai-Liang Feng Ming Wang Qing-Li Zhu Yu-Qin Liu Yu-Xin Jiang Yi Cui |
spellingShingle |
He-Wen Tang Hai-Liang Feng Ming Wang Qing-Li Zhu Yu-Qin Liu Yu-Xin Jiang Yi Cui In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer Chinese Medical Journal |
author_facet |
He-Wen Tang Hai-Liang Feng Ming Wang Qing-Li Zhu Yu-Qin Liu Yu-Xin Jiang Yi Cui |
author_sort |
He-Wen Tang |
title |
In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
title_short |
In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
title_full |
In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
title_fullStr |
In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
title_full_unstemmed |
In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
title_sort |
in vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer |
publisher |
Wolters Kluwer |
series |
Chinese Medical Journal |
issn |
0366-6999 2542-5641 |
publishDate |
2020-01-01 |
description |
Abstract. Background. Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.
Methods. By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hre-gfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).
Results. In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.
Conclusions. The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies. |
url |
http://journals.lww.com/10.1097/CM9.0000000000000616 |
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