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Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts

Background: We developed a fluorophore-conjugated peptide agent, SBK4, that detects a tumor-specific proteolyzed form of the cell adhesion molecule, PTPmu, found in the tumor microenvironment. We previously demonstrated its tissue specific distribution in high-grade brain tumors. To extend those stu...

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Autores principales: Vincent, Jason, Craig, Sonya E. L., Johansen, Mette L., Narla, Jyosthna, Avril, Stefanie, DiFeo, Analisa, Brady-Kalnay, Susann M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911696/
https://www.ncbi.nlm.nih.gov/pubmed/33513911
http://dx.doi.org/10.3390/diagnostics11020181
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author Vincent, Jason
Craig, Sonya E. L.
Johansen, Mette L.
Narla, Jyosthna
Avril, Stefanie
DiFeo, Analisa
Brady-Kalnay, Susann M.
author_facet Vincent, Jason
Craig, Sonya E. L.
Johansen, Mette L.
Narla, Jyosthna
Avril, Stefanie
DiFeo, Analisa
Brady-Kalnay, Susann M.
author_sort Vincent, Jason
collection PubMed
description Background: We developed a fluorophore-conjugated peptide agent, SBK4, that detects a tumor-specific proteolyzed form of the cell adhesion molecule, PTPmu, found in the tumor microenvironment. We previously demonstrated its tissue specific distribution in high-grade brain tumors. To extend those studies to other aggressive solid tumor types, we assessed the tissue distribution of PTPmu/SBK4 in a set of matched gynecologic cancer patient derived xenografts (PDXs) and primary patient tumors, as well as a limited cohort of tumors from gynecological cancer patients. PDXs isolated from the tissues of cancer patients have been shown to yield experimentally manipulatable models that replicate the clinical characteristics of individual patients’ tumors. In this study, gynecological cancer PDXs and patient biopsies were examined to determine if tumor-specific proteolyzed PTPmu was present. Methods: We used the peptide agent SBK4 conjugated to the fluorophore Texas Red (TR) to label tumor tissue microarrays (TMAs) containing patient and/or PDX samples from several high-grade gynecologic cancer types, and quantified the level of staining with Image J. In one TMA, we were able to directly compare the patient and the matched PDX tissue on the same slide. Results: While normal tissue had very little SBK4-TR staining, both primary tumor tissue and PDXs have higher labeling with SBK4-TR. Matched PDXs and patient samples from high-grade endometrial and ovarian cancers demonstrated higher levels of PTPmu by staining with SBK4 than normal tissue. Conclusion: In this sample set, all PDXs and high-grade ovarian cancer samples had increased labeling by SBK4-TR compared with the normal controls. Our results indicate that proteolyzed PTPmu and its novel peptide detection agent, SBK4, allow for the visualization of tumor-specific changes in cell adhesion molecules by tissue-based staining, providing a rationale for further development as an imaging agent in aggressive solid tumors, including gynecological cancers.
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spelling pubmed-79116962021-02-28 Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts Vincent, Jason Craig, Sonya E. L. Johansen, Mette L. Narla, Jyosthna Avril, Stefanie DiFeo, Analisa Brady-Kalnay, Susann M. Diagnostics (Basel) Article Background: We developed a fluorophore-conjugated peptide agent, SBK4, that detects a tumor-specific proteolyzed form of the cell adhesion molecule, PTPmu, found in the tumor microenvironment. We previously demonstrated its tissue specific distribution in high-grade brain tumors. To extend those studies to other aggressive solid tumor types, we assessed the tissue distribution of PTPmu/SBK4 in a set of matched gynecologic cancer patient derived xenografts (PDXs) and primary patient tumors, as well as a limited cohort of tumors from gynecological cancer patients. PDXs isolated from the tissues of cancer patients have been shown to yield experimentally manipulatable models that replicate the clinical characteristics of individual patients’ tumors. In this study, gynecological cancer PDXs and patient biopsies were examined to determine if tumor-specific proteolyzed PTPmu was present. Methods: We used the peptide agent SBK4 conjugated to the fluorophore Texas Red (TR) to label tumor tissue microarrays (TMAs) containing patient and/or PDX samples from several high-grade gynecologic cancer types, and quantified the level of staining with Image J. In one TMA, we were able to directly compare the patient and the matched PDX tissue on the same slide. Results: While normal tissue had very little SBK4-TR staining, both primary tumor tissue and PDXs have higher labeling with SBK4-TR. Matched PDXs and patient samples from high-grade endometrial and ovarian cancers demonstrated higher levels of PTPmu by staining with SBK4 than normal tissue. Conclusion: In this sample set, all PDXs and high-grade ovarian cancer samples had increased labeling by SBK4-TR compared with the normal controls. Our results indicate that proteolyzed PTPmu and its novel peptide detection agent, SBK4, allow for the visualization of tumor-specific changes in cell adhesion molecules by tissue-based staining, providing a rationale for further development as an imaging agent in aggressive solid tumors, including gynecological cancers. MDPI 2021-01-27 /pmc/articles/PMC7911696/ /pubmed/33513911 http://dx.doi.org/10.3390/diagnostics11020181 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vincent, Jason
Craig, Sonya E. L.
Johansen, Mette L.
Narla, Jyosthna
Avril, Stefanie
DiFeo, Analisa
Brady-Kalnay, Susann M.
Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title_full Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title_fullStr Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title_full_unstemmed Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title_short Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts
title_sort detection of tumor-specific ptpmu in gynecological cancer and patient derived xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911696/
https://www.ncbi.nlm.nih.gov/pubmed/33513911
http://dx.doi.org/10.3390/diagnostics11020181
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