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SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model

The cause of death among high-grade serous ovarian cancer (HGSOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Sushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein contai...

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Autores principales: Sheets, Jordan N., Patrick, Mitch E., Egland, Kristi A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299533/
https://www.ncbi.nlm.nih.gov/pubmed/32595828
http://dx.doi.org/10.18632/oncotarget.27626
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author Sheets, Jordan N.
Patrick, Mitch E.
Egland, Kristi A.
author_facet Sheets, Jordan N.
Patrick, Mitch E.
Egland, Kristi A.
author_sort Sheets, Jordan N.
collection PubMed
description The cause of death among high-grade serous ovarian cancer (HGSOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Sushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Previous studies using in vitro methods have indicated that SUSD2 functions as a tumor suppressor in several cancers, including HGSOC. In this study, we generated a HGSOC xenograft mouse model to investigate SUSD2 expression in the context of HGSOC late-stage metastasis and overall survival. OVCAR3 cells with knock-down expression of SUSD2 (OVCAR3 SUSD2-KD) or endogenous expression of SUSD2 (OVCAR3-Non-Targeting (NT)) were injected into the peritoneal cavity of athymic nude mice. Immunohistochemistry analysis was utilized to identify infiltrating cancer cells and metastatic tumors in mouse ovaries, pancreas, spleen, omentum and liver. OVCAR3-NT mice developed significantly less cancer cell infiltrate and tumors in their pancreas and omentum compared to OVCAR3 SUSD2-KD mice. Furthermore, OVCAR3-NT mice displayed a longer median survival when compared to OVCAR3 SUSD2-KD mice (175 days and 185.5 days, respectively; p-value 0.0159). Altogether, the findings generated through the preclinical mouse model suggest that increased SUSD2 expression in HGSOC impedes in vivo metastasis to pancreas and omentum. These results correlate to longer median survival and prove to be consistent with previous findings showing prolonged survival of HGSOC patients with high SUSD2-expressing primary tumors.
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spelling pubmed-72995332020-06-25 SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model Sheets, Jordan N. Patrick, Mitch E. Egland, Kristi A. Oncotarget Research Paper The cause of death among high-grade serous ovarian cancer (HGSOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Sushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Previous studies using in vitro methods have indicated that SUSD2 functions as a tumor suppressor in several cancers, including HGSOC. In this study, we generated a HGSOC xenograft mouse model to investigate SUSD2 expression in the context of HGSOC late-stage metastasis and overall survival. OVCAR3 cells with knock-down expression of SUSD2 (OVCAR3 SUSD2-KD) or endogenous expression of SUSD2 (OVCAR3-Non-Targeting (NT)) were injected into the peritoneal cavity of athymic nude mice. Immunohistochemistry analysis was utilized to identify infiltrating cancer cells and metastatic tumors in mouse ovaries, pancreas, spleen, omentum and liver. OVCAR3-NT mice developed significantly less cancer cell infiltrate and tumors in their pancreas and omentum compared to OVCAR3 SUSD2-KD mice. Furthermore, OVCAR3-NT mice displayed a longer median survival when compared to OVCAR3 SUSD2-KD mice (175 days and 185.5 days, respectively; p-value 0.0159). Altogether, the findings generated through the preclinical mouse model suggest that increased SUSD2 expression in HGSOC impedes in vivo metastasis to pancreas and omentum. These results correlate to longer median survival and prove to be consistent with previous findings showing prolonged survival of HGSOC patients with high SUSD2-expressing primary tumors. Impact Journals LLC 2020-06-16 /pmc/articles/PMC7299533/ /pubmed/32595828 http://dx.doi.org/10.18632/oncotarget.27626 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Sheets et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sheets, Jordan N.
Patrick, Mitch E.
Egland, Kristi A.
SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title_full SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title_fullStr SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title_full_unstemmed SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title_short SUSD2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
title_sort susd2 expression correlates with decreased metastasis and increased survival in a high-grade serous ovarian cancer xenograft murine model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299533/
https://www.ncbi.nlm.nih.gov/pubmed/32595828
http://dx.doi.org/10.18632/oncotarget.27626
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