Peer-reviewed veterinary case report
Zoledronate lowers CXCR4 in dog bone cancer cells affecting spread
By Byrum, M L et al.·Published in Journal of veterinary internal medicine·2016·Department of Veterinary Clinical Medicine, United States·View original on PubMed →
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Original publication title: Downregulation of CXCR4 Expression and Functionality After Zoledronate Exposure in Canine Osteosarcoma.
- Species:
- dog
Plain-English summary
A study found that dogs with osteosarcoma (a type of bone cancer) showed a significant reduction in a specific protein called CXCR4 after treatment with zoledronate, a medication often used to manage bone issues. In 20 dogs treated with zoledronate, the levels of CXCR4 in their tumors decreased by about 40%, which could help slow the spread of cancer. This suggests that zoledronate might not only help with bone health but also potentially impact how the cancer spreads in dogs. If your dog has osteosarcoma, discussing zoledronate treatment with your veterinarian could be beneficial.
People also search for: dog osteosarcoma treatment · zoledronate for dogs · how to slow cancer spread in dogs
Abstract
BACKGROUND: The establishment and progression of metastases remains the life-limiting factor for dogs diagnosed with osteosarcoma (OS). The pattern of metastases is likely regulated through interactions between chemokine receptors and chemokines, and perturbations in these signaling cascades responsible for cytoskeletal organization and directional migration have the potential to alter metastatic cell trafficking behaviors. HYPOTHESIS: Zoledronate will impair directional migration of OS cells through downregulation of chemokine (C-X-C motif) receptor 4 (CXCR4) expression and functionality. SAMPLES: Nineteen archived tumor specimens and plasma from 20 dogs with OS. METHODS: Prospectively, the expressions of CXCR4 were studied in OS cell lines and spontaneous tumor samples. The effect of zoledronate on CXCR4 expression and functionality was investigated by characterizing responses in 3 OS cell lines. In 19 OS specimens and 20 dogs with OS, changes in CXCR4 expression and circulating CXCR4 concentrations were characterized in response to zoledronate therapy respectively. RESULTS: All canine OS cells express CXCR4, and zoledronate reduces CXCR4 expression and functionality by 27.7% (P < .0001), through augmented proteasome degradation and reduced prenylation of heterotrimeric G-proteins in 33% of tumor cell lines evaluated. In OS-bearing dogs, zoledronate reduces CXCR4 expressions by 40% within the primary tumor compared to untreated controls (P = .03) and also decreases the circulating concentrations of CXCR4 in 18 of 20 dogs with OS. CONCLUSIONS AND CLINICAL IMPORTANCE: Zoledronate can alter CXCR4 expression and functionality in OS cells, and consequent perturbations in CXCR4 intracellular signaling cascades might influence patterns of metastases.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/27251585/