Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment
HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bu...
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/7/2171 |
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| author | Sara R. Privatt Owen Ngalamika Jianshui Zhang Qinsheng Li Charles Wood John T. West |
| author_facet | Sara R. Privatt Owen Ngalamika Jianshui Zhang Qinsheng Li Charles Wood John T. West |
| author_sort | Sara R. Privatt |
| collection | DOAJ |
| description | HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein was evaluated for its expression and co-localization with KSHV LANA using multi-color immunofluorescence in KS tissues, KSHV-infected L1T2 cells, uninfected TIVE cells, and murine L1T2 tumor xenografts. Five surface glycoproteins (KDR, FLT4, UNC5A, ADAM12, and CD34) were associated with LANA-positive cells but were also detected in uninfected cells in the KS microenvironment. <i>In vitro</i> L1T2 cultures showed evidence of only FLT4, KDR, and UNC5A, whereas mouse L1T2 xenografts recapitulated human KS cell surface expression profiles, with the exception of CD34 and Prox-1. In KS tumors, most LANA-positive cells co-expressed markers of vascular as well as lymphatic endothelial lineages, suggesting KS-associated dedifferentiation to a more mesenchymal/progenitor phenotype. |
| first_indexed | 2024-03-11T05:40:36Z |
| format | Article |
| id | doaj.art-38e9e5492f1e4767999daa9626f6eb59 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:40:36Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-38e9e5492f1e4767999daa9626f6eb592023-11-17T16:27:10ZengMDPI AGCancers2072-66942023-04-01157217110.3390/cancers15072171Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor MicroenvironmentSara R. Privatt0Owen Ngalamika1Jianshui Zhang2Qinsheng Li3Charles Wood4John T. West5School of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68588, USAUniversity Teaching Hospital, University of Zambia School of Medicine, Lusaka 10101, ZambiaSchool of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68588, USASchool of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68588, USASchool of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68588, USADepartment of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center-New Orleans, New Orleans, LA 70112, USAHIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein was evaluated for its expression and co-localization with KSHV LANA using multi-color immunofluorescence in KS tissues, KSHV-infected L1T2 cells, uninfected TIVE cells, and murine L1T2 tumor xenografts. Five surface glycoproteins (KDR, FLT4, UNC5A, ADAM12, and CD34) were associated with LANA-positive cells but were also detected in uninfected cells in the KS microenvironment. <i>In vitro</i> L1T2 cultures showed evidence of only FLT4, KDR, and UNC5A, whereas mouse L1T2 xenografts recapitulated human KS cell surface expression profiles, with the exception of CD34 and Prox-1. In KS tumors, most LANA-positive cells co-expressed markers of vascular as well as lymphatic endothelial lineages, suggesting KS-associated dedifferentiation to a more mesenchymal/progenitor phenotype.https://www.mdpi.com/2072-6694/15/7/2171Kaposi sarcomaKaposi sarcoma-associated herpesvirusbiomarkertumor microenvironment |
| spellingShingle | Sara R. Privatt Owen Ngalamika Jianshui Zhang Qinsheng Li Charles Wood John T. West Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment Cancers Kaposi sarcoma Kaposi sarcoma-associated herpesvirus biomarker tumor microenvironment |
| title | Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment |
| title_full | Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment |
| title_fullStr | Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment |
| title_full_unstemmed | Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment |
| title_short | Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment |
| title_sort | upregulation of cell surface glycoproteins in correlation with kshv lana in the kaposi sarcoma tumor microenvironment |
| topic | Kaposi sarcoma Kaposi sarcoma-associated herpesvirus biomarker tumor microenvironment |
| url | https://www.mdpi.com/2072-6694/15/7/2171 |
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