The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis
Hypoxia in the tumor microenvironment is a negative prognostic factor associated with tumor progression and metastasis, and therefore represents an attractive therapeutic target for anti-tumor therapy. To test the effectiveness of novel hypoxia-targeting drugs, appropriate preclinical models that re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/5/1093 |
| _version_ | 1797414717974642688 |
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| author | Kelly Harper Anna Yatsyna Martine Charbonneau Karine Brochu-Gaudreau Alexis Perreault Claudio Jeldres Patrick P. McDonald Claire M. Dubois |
| author_facet | Kelly Harper Anna Yatsyna Martine Charbonneau Karine Brochu-Gaudreau Alexis Perreault Claudio Jeldres Patrick P. McDonald Claire M. Dubois |
| author_sort | Kelly Harper |
| collection | DOAJ |
| description | Hypoxia in the tumor microenvironment is a negative prognostic factor associated with tumor progression and metastasis, and therefore represents an attractive therapeutic target for anti-tumor therapy. To test the effectiveness of novel hypoxia-targeting drugs, appropriate preclinical models that recreate tumor hypoxia are essential. The chicken ChorioAllantoic Membrane (CAM) assay is increasingly used as a rapid cost-effective in vivo drug-testing platform that recapitulates many aspects of human cancers. However, it remains to be determined whether this model recreates the hypoxic microenvironment of solid tumors. To detect hypoxia in the CAM model, the hypoxic marker pimonidazole was injected into the vasculature of tumor-bearing CAM, and hypoxia-dependent gene expression was analyzed. We observed that the CAM model effectively supports the development of hypoxic zones in a variety of human tumor cell line-derived and patient’s tumor fragment-derived xenografts. The treatment of both patient and cell line-derived CAM xenografts with modulators of angiogenesis significantly altered the formation of hypoxic zones within the xenografts. Furthermore, the changes in hypoxia translated into modulated levels of chick liver metastasis as measured by Alu-based assay. These findings demonstrate that the CAM xenograft model is a valuable in vivo platform for studying hypoxia that could facilitate the identification and testing of drugs targeting this tumor microenvironment. |
| first_indexed | 2024-03-09T05:37:37Z |
| format | Article |
| id | doaj.art-5142d1c732e54ddcb10e9c8f9c03a166 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:37:37Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5142d1c732e54ddcb10e9c8f9c03a1662023-12-03T12:27:09ZengMDPI AGCancers2072-66942021-03-01135109310.3390/cancers13051093The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and MetastasisKelly Harper0Anna Yatsyna1Martine Charbonneau2Karine Brochu-Gaudreau3Alexis Perreault4Claudio Jeldres5Patrick P. McDonald6Claire M. Dubois7Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Medicine, Pulmonary Division, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, CanadaHypoxia in the tumor microenvironment is a negative prognostic factor associated with tumor progression and metastasis, and therefore represents an attractive therapeutic target for anti-tumor therapy. To test the effectiveness of novel hypoxia-targeting drugs, appropriate preclinical models that recreate tumor hypoxia are essential. The chicken ChorioAllantoic Membrane (CAM) assay is increasingly used as a rapid cost-effective in vivo drug-testing platform that recapitulates many aspects of human cancers. However, it remains to be determined whether this model recreates the hypoxic microenvironment of solid tumors. To detect hypoxia in the CAM model, the hypoxic marker pimonidazole was injected into the vasculature of tumor-bearing CAM, and hypoxia-dependent gene expression was analyzed. We observed that the CAM model effectively supports the development of hypoxic zones in a variety of human tumor cell line-derived and patient’s tumor fragment-derived xenografts. The treatment of both patient and cell line-derived CAM xenografts with modulators of angiogenesis significantly altered the formation of hypoxic zones within the xenografts. Furthermore, the changes in hypoxia translated into modulated levels of chick liver metastasis as measured by Alu-based assay. These findings demonstrate that the CAM xenograft model is a valuable in vivo platform for studying hypoxia that could facilitate the identification and testing of drugs targeting this tumor microenvironment.https://www.mdpi.com/2072-6694/13/5/1093hypoxiaChorioAllantoic Membranechick embryometastasistumor progression |
| spellingShingle | Kelly Harper Anna Yatsyna Martine Charbonneau Karine Brochu-Gaudreau Alexis Perreault Claudio Jeldres Patrick P. McDonald Claire M. Dubois The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis Cancers hypoxia ChorioAllantoic Membrane chick embryo metastasis tumor progression |
| title | The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis |
| title_full | The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis |
| title_fullStr | The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis |
| title_full_unstemmed | The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis |
| title_short | The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis |
| title_sort | chicken chorioallantoic membrane tumor assay as a relevant in vivo model to study the impact of hypoxia on tumor progression and metastasis |
| topic | hypoxia ChorioAllantoic Membrane chick embryo metastasis tumor progression |
| url | https://www.mdpi.com/2072-6694/13/5/1093 |
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