TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role

Maria Isabel Carvalho ¹, Ricardo Silva-Carvalho ^2,3, Justina Prada ^4,5

⁰MVET Research in Veterinary Medicine. Faculty of Veterinary Medicine, Lusófona University - Lisbon Centre, Lisboa, Portugal.

The Veterinary Quarterly +

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August 21, 2024

View abstract on PubMed

Summary

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are key in canine mammary tumors (CMT). High TGFβ levels correlate with aggressive features and poor survival, suggesting they are potential therapeutic targets.

Area Of Science

Veterinary Oncology
Immunology
Cancer Biology

Background

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Tregs) are implicated in human breast cancer progression.
The role of these factors in canine mammary tumors (CMTs) is not well-established.
Understanding these pathways in CMTs could reveal novel therapeutic targets.

Purpose Of The Study

To investigate the expression of TGFβ in malignant CMTs.
To evaluate the correlation between TGFβ expression and FoxP3, VEGF, and CD31 markers.
To assess the association of TGFβ with clinicopathologic parameters and overall survival in CMT patients.

Main Methods

Immunohistochemistry was used to assess tumoral TGFβ expression in 67 malignant CMT samples.
Correlation analysis was performed between TGFβ levels and previously determined FoxP3, VEGF, and CD31 markers.
Statistical analysis was conducted to evaluate associations with clinicopathologic parameters and overall survival.

Main Results

High TGFβ levels were significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), intravascular emboli, and lymph node metastases.
TGFβ expression showed a strong positive correlation with FoxP3, a weak correlation with VEGF, and a moderate correlation with CD31.
Concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 was linked to increased tumor malignancy and shorter overall survival.
Lymph node metastasis independently predicted an 11-fold increased risk of disease-related death.

Conclusions

TGFβ and Treg cells play a significant role in canine mammary tumor progression.
The combined high expression of TGFβ with FoxP3, VEGF, or CD31 indicates aggressive tumor behavior.
TGFβ and Treg cells represent promising targets for future canine cancer immunotherapy strategies.

Keywords:

Angiogenesis CD31 FoxP3 TGFβ Treg cells VEGF canine mammary tumors prognosis

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