Activation of TLR4/NF-κB/TNF-α pathway in inflammation and apoptosis during stable and progressive phases of canine transmissible venereal tumors

Background Canine Transmissible Venereal Tumor (CTVT) is a clonally transmissible, low-grade malignant round-cell tumor that affects dogs of all ages and breeds. Although malignant due to its invasive potential and occasional metastasis, it differs from classical malignancies by its unique ability to undergo spontaneous regression, leading some authors to describe it as benign-like. CTVT progresses through progressive (P), stable (S), and regressive (R) phases. The P phase is characterized by rapid tumor proliferation, while the S phase shows arrested growth and unchanged lesions. Despite numerous studies, the molecular mechanisms underlying these transitions remain incompletely understood. Aim This study aimed to evaluate the role of the TLR4/NF-kappa B/TNF-alpha signaling pathway in the P and S phases of CTVT. Methodology Tumor samples from 12 CTVT-positive dogs were classified into P and S phases (n = 6 each) based on histopathology. Expression of TLR4, NF-kappa B, TNF-alpha, CD4, IL-1 beta, IL-6, IL-10, Bcl-2, BAX, and Caspase-3 was assessed using immunohistochemistry and immunofluorescence. Results All parameters examined (except Bcl-2) were found to increase statistically significantly (p < 0.0001) in the S phase compared to the P phase. Bcl-2 expression was found to be significantly higher in the P phase compared to the S phase (p < 0.0001). Furthermore, the TLR4/NF-kappa B/TNF-alpha pathway showed stronger activation in the S phase compared to the P phase. This was associated with enhanced inflammation and apoptosis, as reflected by higher expression of pro-inflammatory cytokines and apoptotic markers. Conclusion Our findings suggest that during the S phase of CTVT, the immune response is more actively mediated by the TLR4/NF-kappa B/TNF-alpha pathway compared to the P phase. These results provide insights into the immunopathogenesis of CTVT and highlight the potential role of inflammatory and apoptotic signaling in tumor stabilization.

Dergi

TISSUE & CELL

Yıl

2026

Cilt

98

ISSN

0040-8166

DOI

10.1016/j.tice.2025.103193

WoS UID

WOS:001607416900001