Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts
Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, deri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/3/579 |
| _version_ | 1797714568988852224 |
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| author | Vui King Vincent-Chong Mukund Seshadri |
| author_facet | Vui King Vincent-Chong Mukund Seshadri |
| author_sort | Vui King Vincent-Chong |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD<sub>50</sub> for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease. |
| first_indexed | 2024-03-12T07:54:52Z |
| format | Article |
| id | doaj.art-5ee097f180c746618a59ec4d65e34002 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:54:52Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5ee097f180c746618a59ec4d65e340022023-09-02T20:22:12ZengMDPI AGCancers2072-66942020-03-0112357910.3390/cancers12030579cancers12030579Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic AllograftsVui King Vincent-Chong0Mukund Seshadri1Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAOral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD<sub>50</sub> for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease.https://www.mdpi.com/2072-6694/12/3/579oral cancersquamous cell carcinomaradiation therapyorganoidsorthotopic osccmagnetic resonance imaging |
| spellingShingle | Vui King Vincent-Chong Mukund Seshadri Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts Cancers oral cancer squamous cell carcinoma radiation therapy organoids orthotopic oscc magnetic resonance imaging |
| title | Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts |
| title_full | Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts |
| title_fullStr | Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts |
| title_full_unstemmed | Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts |
| title_short | Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts |
| title_sort | development and radiation response assessment in a novel syngeneic mouse model of tongue cancer 2d culture 3d organoids and orthotopic allografts |
| topic | oral cancer squamous cell carcinoma radiation therapy organoids orthotopic oscc magnetic resonance imaging |
| url | https://www.mdpi.com/2072-6694/12/3/579 |
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