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A Next-generation Tissue Microarray ngTMA Protocol for Biomarker Studies
Published on: September 23, 2014
Cancer-testis antigen expression in canine melanoma and healthy tissues
Esther Hindriks1, Wilhelmina Bergmann2, Aitor Martínez Ruiz2
1Faculty of Veterinary Medicine, Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Utrecht University, Utrecht, the Netherlands.
Abstract:
Cancer-testis antigens (CTAs) are promising targets for immuno-oncotherapy. They offer the potential to treat cancers for which effective systemic therapies are lacking, including canine malignant melanoma (CMM). In this study, we investigate the suitability of eight canine orthologs of human CTAs as targets for immunotherapy, including cancer-associated gene 1 (CAGE1), CCCTC-binding factor (CTCFL), DEAD-box helicase 53 (DDX53), the melanoma antigen gene (MAGE), 5'-nucleotidase, cytosolic IB (NT5C1B), P antigen family member 3-like (PAGE3-like), preferentially expressed antigen in melanoma (PRAME), and synovial sarcoma X chromosome breakpoint (SSX). MAGE proteins were detected by immunohistochemistry in 12.1 % (4/33) of CMM cases, including digital and oral melanoma, with healthy tissue expression restricted to the testis. CTA mRNA was detected by Real-time PCR in canine testis and validated through gel electrophoresis and Sanger sequencing. MAGE, PAGE3-like, and PRAME mRNA were strongly expressed in canine oral melanoma and metastatic cell lines with restricted expression in normal tissues. CAGE1, CTCFL, DDX53, and SSX6 were only weakly expressed or absent in canine oral melanoma. CTCFL and DDX53 expression in healthy tissues was not restricted to the testis, as moderate expression was found in the kidney. These results suggest that dogs express CTAs, similar to humans, and thus CTAs may serve as a target for immunotherapy in dogs.
Insights
Cancer-testis antigens (CTAs) show promise for canine cancer immunotherapy. Researchers found MAGE, PAGE3-like, and PRAME CTA expression in canine malignant melanoma, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Cancer-testis antigens (CTAs) are recognized as potential targets for cancer immunotherapy.
- Canine malignant melanoma (CMM) is an aggressive cancer lacking effective systemic treatments.
- Investigating canine CTA expression is crucial for developing novel immunotherapies.
Purpose of the Study:
- To evaluate eight canine orthologs of human CTAs as potential immunotherapy targets for CMM.
- To determine the expression patterns of selected CTAs in CMM and healthy canine tissues.
Main Methods:
- Immunohistochemistry was used to detect MAGE protein expression in CMM samples.
- Real-time PCR, gel electrophoresis, and Sanger sequencing were employed to analyze CTA mRNA expression in canine tissues and cell lines.
- Expression analysis was performed in canine oral melanoma, metastatic cell lines, and healthy tissues, including the testis and kidney.
Main Results:
- MAGE proteins were found in 12.1% of CMM cases, with normal expression limited to the testis.
- MAGE, PAGE3-like, and PRAME mRNA showed strong expression in canine oral melanoma and metastatic cell lines, with restricted normal tissue expression.
- CAGE1, CTCFL, DDX53, and SSX6 showed weak or absent expression in canine oral melanoma; CTCFL and DDX53 were also expressed in healthy kidney tissue.
Conclusions:
- Canine malignant melanoma expresses specific cancer-testis antigens (CTAs), including MAGE, PAGE3-like, and PRAME.
- These CTAs exhibit restricted expression in normal tissues, making them suitable targets for canine immunotherapy.
- The findings support the potential of CTAs as targets for novel immuno-oncotherapy strategies in dogs.
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