A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin
Merkel cell polyomavirus (MCPyV) is a human polyomavirus causally linked to the development of Merkel cell carcinoma (MCC), an aggressive malignancy that largely arises within the dermis of the skin. In this study, we recapitulate the histopathology of human MCC tumors in vitro using an organotypic...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/1/138 |
| _version_ | 1797409570922954752 |
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| author | Amanda S. W. Loke B. Jack Longley Paul F. Lambert Megan E. Spurgeon |
| author_facet | Amanda S. W. Loke B. Jack Longley Paul F. Lambert Megan E. Spurgeon |
| author_sort | Amanda S. W. Loke |
| collection | DOAJ |
| description | Merkel cell polyomavirus (MCPyV) is a human polyomavirus causally linked to the development of Merkel cell carcinoma (MCC), an aggressive malignancy that largely arises within the dermis of the skin. In this study, we recapitulate the histopathology of human MCC tumors in vitro using an organotypic (raft) culture system that is traditionally used to recapitulate the dermal and epidermal equivalents of skin in three dimensions (3D). In the optimal culture condition, MCPyV+ MCC cells were embedded in collagen between the epidermal equivalent comprising human keratinocytes and a dermal equivalent containing fibroblasts, resulting in MCC-like lesions arising within the dermal equivalent. The presence and organization of MCC cells within these dermal lesions were characterized through biomarker analyses. Interestingly, co-culture of MCPyV+ MCC together with keratinocytes specifically within the epidermal equivalent of the raft did not reproduce human MCC morphology, nor were any keratinocytes necessary for MCC-like lesions to develop in the dermal equivalent. This 3D tissue culture system provides a novel in vitro platform for studying the role of MCPyV T antigens in MCC oncogenesis, identifying additional factors involved in this process, and for screening potential MCPyV+ MCC therapeutic strategies. |
| first_indexed | 2024-03-09T04:17:28Z |
| format | Article |
| id | doaj.art-e4feb725d9bc4068be28c48992c16156 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T04:17:28Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e4feb725d9bc4068be28c48992c161562023-12-03T13:52:44ZengMDPI AGViruses1999-49152021-01-0113113810.3390/v13010138A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human SkinAmanda S. W. Loke0B. Jack Longley1Paul F. Lambert2Megan E. Spurgeon3McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI 53705, USADepartment of Dermatology, University of Wisconsin School of Medicine & Public Health, Madison, WI 53705, USAMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI 53705, USAMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI 53705, USAMerkel cell polyomavirus (MCPyV) is a human polyomavirus causally linked to the development of Merkel cell carcinoma (MCC), an aggressive malignancy that largely arises within the dermis of the skin. In this study, we recapitulate the histopathology of human MCC tumors in vitro using an organotypic (raft) culture system that is traditionally used to recapitulate the dermal and epidermal equivalents of skin in three dimensions (3D). In the optimal culture condition, MCPyV+ MCC cells were embedded in collagen between the epidermal equivalent comprising human keratinocytes and a dermal equivalent containing fibroblasts, resulting in MCC-like lesions arising within the dermal equivalent. The presence and organization of MCC cells within these dermal lesions were characterized through biomarker analyses. Interestingly, co-culture of MCPyV+ MCC together with keratinocytes specifically within the epidermal equivalent of the raft did not reproduce human MCC morphology, nor were any keratinocytes necessary for MCC-like lesions to develop in the dermal equivalent. This 3D tissue culture system provides a novel in vitro platform for studying the role of MCPyV T antigens in MCC oncogenesis, identifying additional factors involved in this process, and for screening potential MCPyV+ MCC therapeutic strategies.https://www.mdpi.com/1999-4915/13/1/138Merkel cell polyomavirusMerkel cell carcinomaMerkel cellsDNA tumor virushuman polyomavirusorganotypic rafts |
| spellingShingle | Amanda S. W. Loke B. Jack Longley Paul F. Lambert Megan E. Spurgeon A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin Viruses Merkel cell polyomavirus Merkel cell carcinoma Merkel cells DNA tumor virus human polyomavirus organotypic rafts |
| title | A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin |
| title_full | A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin |
| title_fullStr | A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin |
| title_full_unstemmed | A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin |
| title_short | A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin |
| title_sort | novel in vitro culture model system to study merkel cell polyomavirus associated mcc using three dimensional organotypic raft equivalents of human skin |
| topic | Merkel cell polyomavirus Merkel cell carcinoma Merkel cells DNA tumor virus human polyomavirus organotypic rafts |
| url | https://www.mdpi.com/1999-4915/13/1/138 |
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