Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer
Mesothelin (MSLN) overexpression (OE) is a frequent finding in ovarian carcinomas and increases cell survival and tumor aggressiveness. Since cancer stem cells (CSCs) contribute to pathogenesis, chemoresistance and malignant behavior in ovarian cancer (OC), we hypothesized that MSLN expression could...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1016 |
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| author | Mariana Nunes Francisca Pacheco Ricardo Coelho Dina Leitão Sara Ricardo Leonor David |
| author_facet | Mariana Nunes Francisca Pacheco Ricardo Coelho Dina Leitão Sara Ricardo Leonor David |
| author_sort | Mariana Nunes |
| collection | DOAJ |
| description | Mesothelin (MSLN) overexpression (OE) is a frequent finding in ovarian carcinomas and increases cell survival and tumor aggressiveness. Since cancer stem cells (CSCs) contribute to pathogenesis, chemoresistance and malignant behavior in ovarian cancer (OC), we hypothesized that MSLN expression could be creating a favorable environment that nurtures CSCs. In this study, we analyzed the expression of MSLN and CSC markers SOX2 and ALDH1 by immunohistochemistry (IHC) in different model systems: primary high-grade serous carcinomas (HGSCs) and OC cell lines, including cell lines that were genetically engineered for MSLN expression by either CRISPR-Cas9-mediated knockout (Δ) or lentivirus-mediated OE. Cell lines, wild type and genetically engineered, were evaluated in 2D and 3D culture conditions and xenografted in nude mice. We observed that MSLN was widely expressed in HGSC, and restricted expression was observed in OC cell lines. In contrast, SOX2 and ALDH1 expression was limited in all tissue and cell models. Most importantly, the expression of CSC markers was independent of MSLN expression, and manipulation of MSLN expression did not affect CSC markers. In conclusion, MSLN expression is not involved in driving the CSC phenotype. |
| first_indexed | 2024-03-09T23:51:28Z |
| format | Article |
| id | doaj.art-492d0931295f4109a5878f2ffb6b6ee7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:51:28Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-492d0931295f4109a5878f2ffb6b6ee72023-11-23T16:33:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233101610.3390/ijms23031016Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian CancerMariana Nunes0Francisca Pacheco1Ricardo Coelho2Dina Leitão3Sara Ricardo4Leonor David5Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, PortugalDifferentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, PortugalOvarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, CH-4031 Basel, SwitzerlandDepartment of Pathology, Medical Faculty of the University of Porto (FMUP), 4200-319 Porto, PortugalDifferentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, PortugalDifferentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, PortugalMesothelin (MSLN) overexpression (OE) is a frequent finding in ovarian carcinomas and increases cell survival and tumor aggressiveness. Since cancer stem cells (CSCs) contribute to pathogenesis, chemoresistance and malignant behavior in ovarian cancer (OC), we hypothesized that MSLN expression could be creating a favorable environment that nurtures CSCs. In this study, we analyzed the expression of MSLN and CSC markers SOX2 and ALDH1 by immunohistochemistry (IHC) in different model systems: primary high-grade serous carcinomas (HGSCs) and OC cell lines, including cell lines that were genetically engineered for MSLN expression by either CRISPR-Cas9-mediated knockout (Δ) or lentivirus-mediated OE. Cell lines, wild type and genetically engineered, were evaluated in 2D and 3D culture conditions and xenografted in nude mice. We observed that MSLN was widely expressed in HGSC, and restricted expression was observed in OC cell lines. In contrast, SOX2 and ALDH1 expression was limited in all tissue and cell models. Most importantly, the expression of CSC markers was independent of MSLN expression, and manipulation of MSLN expression did not affect CSC markers. In conclusion, MSLN expression is not involved in driving the CSC phenotype.https://www.mdpi.com/1422-0067/23/3/1016high-grade serous carcinomamesothelinSOX2ALDH1cancer stem cells |
| spellingShingle | Mariana Nunes Francisca Pacheco Ricardo Coelho Dina Leitão Sara Ricardo Leonor David Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer International Journal of Molecular Sciences high-grade serous carcinoma mesothelin SOX2 ALDH1 cancer stem cells |
| title | Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer |
| title_full | Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer |
| title_fullStr | Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer |
| title_full_unstemmed | Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer |
| title_short | Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer |
| title_sort | mesothelin expression is not associated with the presence of cancer stem cell markers sox2 and aldh1 in ovarian cancer |
| topic | high-grade serous carcinoma mesothelin SOX2 ALDH1 cancer stem cells |
| url | https://www.mdpi.com/1422-0067/23/3/1016 |
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