Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intrap...

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Autores principales:	Tyvette S. Hilliard, Brooke Kowalski, Kyle Iwamoto, Elizabeth A. Agadi, Yueying Liu, Jing Yang, Marwa Asem, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, Gifty Marfowaa, Madeleine G. Yemc, Phillip Petrasko, M. Sharon Stack
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ovarian cancer metastasis mesothelium mesothelin cell adhesion collagen Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c13afbf1f05f4c64aad9f7c5b4e9fc4f
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spelling	oai:doaj.org-article:c13afbf1f05f4c64aad9f7c5b4e9fc4f2021-11-25T17:56:40ZHost Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment10.3390/ijms2222124431422-00671661-6596https://doaj.org/article/c13afbf1f05f4c64aad9f7c5b4e9fc4f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12443https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLN<sup>KO</sup>). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLN<sup>KO</sup> mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLN<sup>WT</sup>) or MSLN<sup>KO</sup> mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLN<sup>KO</sup> mice compared to MSLN<sup>WT</sup> mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.Tyvette S. HilliardBrooke KowalskiKyle IwamotoElizabeth A. AgadiYueying LiuJing YangMarwa AsemYuliya KlymenkoJeff JohnsonZonggao ShiGifty MarfowaaMadeleine G. YemcPhillip PetraskoM. Sharon StackMDPI AGarticleovarian cancermetastasismesotheliummesothelincell adhesioncollagenBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12443, p 12443 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian cancer metastasis mesothelium mesothelin cell adhesion collagen Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ovarian cancer metastasis mesothelium mesothelin cell adhesion collagen Biology (General) QH301-705.5 Chemistry QD1-999 Tyvette S. Hilliard Brooke Kowalski Kyle Iwamoto Elizabeth A. Agadi Yueying Liu Jing Yang Marwa Asem Yuliya Klymenko Jeff Johnson Zonggao Shi Gifty Marfowaa Madeleine G. Yemc Phillip Petrasko M. Sharon Stack Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
description	Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLN<sup>KO</sup>). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLN<sup>KO</sup> mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLN<sup>WT</sup>) or MSLN<sup>KO</sup> mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLN<sup>KO</sup> mice compared to MSLN<sup>WT</sup> mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.
format	article
author	Tyvette S. Hilliard Brooke Kowalski Kyle Iwamoto Elizabeth A. Agadi Yueying Liu Jing Yang Marwa Asem Yuliya Klymenko Jeff Johnson Zonggao Shi Gifty Marfowaa Madeleine G. Yemc Phillip Petrasko M. Sharon Stack
author_facet	Tyvette S. Hilliard Brooke Kowalski Kyle Iwamoto Elizabeth A. Agadi Yueying Liu Jing Yang Marwa Asem Yuliya Klymenko Jeff Johnson Zonggao Shi Gifty Marfowaa Madeleine G. Yemc Phillip Petrasko M. Sharon Stack
author_sort	Tyvette S. Hilliard
title	Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
title_short	Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
title_full	Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
title_fullStr	Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
title_full_unstemmed	Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment
title_sort	host mesothelin expression increases ovarian cancer metastasis in the peritoneal microenvironment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c13afbf1f05f4c64aad9f7c5b4e9fc4f
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Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

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