Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma

BackgroundAlthough metastasis-associated protein 1 (MTA1) is known to play a role in cancer invasion and metastasis of various cancers, the clinical significance of its expression in canine urothelial carcinoma (UC) has not been explored. We sought to evaluate the expression of MTA1, cyclooxygenase...

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Main Authors: Gisella Campanelli, Noah Waxner, Nema Parkhomovsky, Chun Kuen Mak, Ji-Hang Yin, Susanne Je-Han Lin, Raphael Vanderstichel, Ching Yang, Anait S. Levenson
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1527167/full
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author Gisella Campanelli
Noah Waxner
Nema Parkhomovsky
Chun Kuen Mak
Ji-Hang Yin
Susanne Je-Han Lin
Raphael Vanderstichel
Ching Yang
Anait S. Levenson
author_facet Gisella Campanelli
Noah Waxner
Nema Parkhomovsky
Chun Kuen Mak
Ji-Hang Yin
Susanne Je-Han Lin
Raphael Vanderstichel
Ching Yang
Anait S. Levenson
author_sort Gisella Campanelli
collection DOAJ
description BackgroundAlthough metastasis-associated protein 1 (MTA1) is known to play a role in cancer invasion and metastasis of various cancers, the clinical significance of its expression in canine urothelial carcinoma (UC) has not been explored. We sought to evaluate the expression of MTA1, cyclooxygenase 2 (COX2) and E-cadherin (E-cad) in association with clinicopathological parameters in clinical samples of canine UC.MethodsWe retrospectively analyzed UC tissues from 28 canine patients using immunohistochemistry for Ki67, CD31, MTA1, COX2, and E-cad staining. Statistical significance for marker staining intensities was evaluated by ANOVA or Student’s t-test. The correlation between molecular markers in canine UC samples detected by IHC and clinicopathological features was calculated by the Wilcoxon (Mann–Whitney) and Kruskal-Wallis tests. Western blot analysis was performed for detection of EMT markers in canine cell lines.ResultsWe show that MTA1 and COX2 are overexpressed in canine UC samples compared to normal canine bladder samples, whereas E-cad levels are higher in normal bladder. The results demonstrated that MTA1 expression correlated with aggressive clinicopathological features such as high tumor-grade, muscular/vascular invasion, and metastasis. The expression of MTA1 differed in tumors depending on their localization, with the highest being in the urethra adjoining the prostate. Unexpectedly, higher E-cad levels were detected in metastatic tumor cells compared to primary tumor cells.ConclusionThese findings suggest that MTA1 may represent a key upstream effector tightly associated with COX2 and E-cad-mediated events in canine UC. Accordingly, MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment.
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spelling doaj-art-67f73a6b523048ef9eaa973f057263cd2025-08-20T02:28:16ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-04-011210.3389/fvets.2025.15271671527167Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinomaGisella Campanelli0Noah Waxner1Nema Parkhomovsky2Chun Kuen Mak3Ji-Hang Yin4Susanne Je-Han Lin5Raphael Vanderstichel6Ching Yang7Anait S. Levenson8Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesDepartment of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesCollege of Sciences, Long Island University, Brookville, NY, United StatesDepartment of Veterinary Clinical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Veterinary Clinical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesDepartment of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesDepartment of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY, United StatesBackgroundAlthough metastasis-associated protein 1 (MTA1) is known to play a role in cancer invasion and metastasis of various cancers, the clinical significance of its expression in canine urothelial carcinoma (UC) has not been explored. We sought to evaluate the expression of MTA1, cyclooxygenase 2 (COX2) and E-cadherin (E-cad) in association with clinicopathological parameters in clinical samples of canine UC.MethodsWe retrospectively analyzed UC tissues from 28 canine patients using immunohistochemistry for Ki67, CD31, MTA1, COX2, and E-cad staining. Statistical significance for marker staining intensities was evaluated by ANOVA or Student’s t-test. The correlation between molecular markers in canine UC samples detected by IHC and clinicopathological features was calculated by the Wilcoxon (Mann–Whitney) and Kruskal-Wallis tests. Western blot analysis was performed for detection of EMT markers in canine cell lines.ResultsWe show that MTA1 and COX2 are overexpressed in canine UC samples compared to normal canine bladder samples, whereas E-cad levels are higher in normal bladder. The results demonstrated that MTA1 expression correlated with aggressive clinicopathological features such as high tumor-grade, muscular/vascular invasion, and metastasis. The expression of MTA1 differed in tumors depending on their localization, with the highest being in the urethra adjoining the prostate. Unexpectedly, higher E-cad levels were detected in metastatic tumor cells compared to primary tumor cells.ConclusionThese findings suggest that MTA1 may represent a key upstream effector tightly associated with COX2 and E-cad-mediated events in canine UC. Accordingly, MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment.https://www.frontiersin.org/articles/10.3389/fvets.2025.1527167/fullcanine urothelial carcinomacanine cell linesimmunohistochemistryMTA1COX2E-cadherin
spellingShingle Gisella Campanelli
Noah Waxner
Nema Parkhomovsky
Chun Kuen Mak
Ji-Hang Yin
Susanne Je-Han Lin
Raphael Vanderstichel
Ching Yang
Anait S. Levenson
Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
Frontiers in Veterinary Science
canine urothelial carcinoma
canine cell lines
immunohistochemistry
MTA1
COX2
E-cadherin
title Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
title_full Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
title_fullStr Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
title_full_unstemmed Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
title_short Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma
title_sort identification of metastasis associated protein 1 mta1 as a new molecular marker for canine urothelial carcinoma
topic canine urothelial carcinoma
canine cell lines
immunohistochemistry
MTA1
COX2
E-cadherin
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1527167/full
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