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. 2023 Sep;21(3):559-564.
doi: 10.1111/vco.12903. Epub 2023 May 6.

Antioxidant 1 copper chaperone gene expression and copper levels in dog osteosarcoma patients

Pedro L Rivera  1 , William T Li  2 , Sumail Bhogal  2 , Jonathan B Mandell  2 , Rebekah Belayneh  2 , Margaret L Hankins  2 , John T Payne  1 , Rebecca J Watters  2 , Kurt R Weiss  2
Affiliations

Antioxidant 1 copper chaperone gene expression and copper levels in dog osteosarcoma patients

Pedro L Rivera et al. Vet Comp Oncol. 2023 Sep.

Abstract

Twenty-four dogs with OS underwent limb amputation. Serum, OS tumour, and normal bone were harvested at time of surgery. RNA was extracted and gene expression was performed using quantitative polymerase chain reaction (qPCR). Tissue and blood copper concentrations were also determined with spectrophotometry. Compared to bone, tumour samples had significantly higher expressions of antioxidant 1 copper chaperone (ATOX1, p = .0003). OS tumour copper levels were significantly higher than that of serum (p < .010) and bone (p = .038). Similar to our previous observations in mouse and human OS, dog OS demonstrates overexpression of genes that regulate copper metabolism (ATOX1), and subsequent copper levels. Dogs with OS may provide a robust comparative oncology platform for the further study of these factors, as well as potential pharmacologic interventions.

Keywords: ALDH; canine; copper; osteosarcoma.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors have no conflict of interest, disclaimers or source of support to disclose.

Figures

FIGURE 1
FIGURE 1
Fold change of genes ALDH1A1, CRT1, ATOX1, and ATP7B between normal bone and tumour samples. Our data demonstrate gene expression differences between normal bone (blue bars) and OS (red bars). While several factors trended to greater expression in tumours compared with normal bone, only ATOX1 reached statistical significance (p = .0003). Values are depicted as mean and standard deviation. These findings are commensurate with our previously published observations in murine and human OS cells and tissues.,,–
FIGURE 2
FIGURE 2
Copper levels: Copper levels in canine OS cells are increased compared to serum and normal bone. Average copper levels of serum (505 ng/mL, SD = 124.62) and bone (576 ng/mg, SD = 268.72) were not statistically significant from each other (p = 0.724). However, average copper levels found in OS tumour samples was 809 ng/mg (SD = 452.98), significantly higher than that of both serum (p < .010) and bone (p = .038).
See this image and copyright information in PMC

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