Peer-reviewed veterinary case report
Hedgehog pathway role and blocking effects in dog bone cancer cells
By Nam, Aryung et al.·Published in Veterinary and comparative oncology·2022·Department of Veterinary Internal Medicine, South Korea·View original on PubMed →
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Original publication title: Expression of the hedgehog signalling pathway and the effect of inhibition at the level of smoothened in canine osteosarcoma cell lines.
- Species:
- dog
Plain-English summary
A study found that a common bone cancer in dogs, called osteosarcoma, shows abnormal activity in a specific signaling pathway known as the hedgehog (Hh) pathway. Researchers tested a drug called cyclopamine, which blocks a part of this pathway, on different canine osteosarcoma cell lines. They discovered that cyclopamine significantly reduced the growth and survival of these cancer cells, especially in one cell line that was particularly sensitive to the treatment. This suggests that targeting the Hh pathway could be a promising new approach for treating osteosarcoma in dogs.
People also search for: dog osteosarcoma treatment · cyclopamine for dog cancer · canine bone cancer symptoms
Abstract
Osteosarcoma (OSA) is the most common malignant bone cancer in dogs. Canine and human OSA share several features, including tumour environments, response to traditional treatment, and several molecular pathways. Hedgehog (Hh) signalling is known to contribute to tumorigenesis and progression of various cancers, including human OSA. This study aimed to identify the role of the Hh signalling pathway in canine OSA cell lines, including Abrams, D17, and Moresco, focusing on the signal transducer Smoothened (SMO). mRNA and protein levels of Hh pathway components, including SHH, IHH, SMO, and PTCH1, were aberrant in all examined OSA cell lines compared with canine osteoblast cells. The SMO inhibitor cyclopamine significantly decreased cell viability and colony-forming ability in the canine OSA cell lines in a dose-dependent manner. Moresco cells, which expressed the highest level of SMO protein, were the most sensitive to the anticancer effect of cyclopamine among the three canine OSA cell lines tested. Hh downstream target gene and protein expression in canine OSA cell lines were downregulated after cyclopamine treatment. In addition, cyclopamine significantly increased apoptotic cell death in Abrams and Moresco cells. The findings that Hh/SMO is activated in canine OSA cell lines and cyclopamine suppresses OSA cell survival via inhibition of SMO suggest that the Hh/SMO signalling pathway might be a novel therapeutic target for canine OSA.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/35521940/