Expression Profiling of Selected Immune Genes and Trabecular Microarchitecture in Breast Cancer Skeletal Metastases Model: Effect of α-Tocopherol Acetate Supplementation

Abstract

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 10⁴) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion, BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.

Keywords: Bone metastases; COX-2; Microarchitecture; TNF-α; Walker 256/B malignant breast cancer; α-Tocopherol acetate.