Affiliation:
1. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
2. Department of Microbiology & Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
Abstract
Despite the advancements in treatments for other cancers, the outcomes for osteosarcoma (OSA) patients have not improved in the past forty years, especially in metastatic patients. Moreover, the major cause of death in OSA patients is due to metastatic lesions. In the current study, we report on the establishment of three cell lines derived from metastatic canine OSA patients and their transcriptome as compared to normal canine osteoblasts. All the OSA cell lines displayed significant upregulation of genes in the epithelial mesenchymal transition (EMT) pathway, and upregulation of key cytokines such as CXCL8, CXCL10 and IL6. The two most upregulated genes are MX1 and ISG15. Interestingly, ISG15 has recently been identified as a potential therapeutic target for OSA. In addition, there is notable downregulation of cell cycle control genes, including CDKN2A, CDKN2B and THBS1. At the protein level, p16INK4A, coded by CDKN2A, was undetectable in all the canine OSA cell lines, while expression of the tumor suppressor PTEN was variable, with one cell line showing complete absence and others showing low levels of expression. In addition, the cells express a variety of actionable genes, including KIT, ERBB2, VEGF and immune checkpoint genes. These findings, similar to those reported in human OSA, point to some genes that can be used for prognosis, targeted therapies and novel drug development for both canine and human OSA patients.
Funder
Michigan State University
Reference91 articles.
1. Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program;Mirabello;Cancer,2009
2. Withrow, S.J., and MacEwen, E.G. (2001). Small Animal Clinical Oncology, W. B. Saunders. [3rd ed.].
3. Dog models of naturally occurring cancer;Rowell;Trends Mol. Med.,2011
4. Breed-specific incidence rates of canine primary bone tumors—A population based survey of dogs in Norway;Anfinsen;Can. J. Vet. Res.,2011
5. Yang, Y.T., and Yuzbasiyan-Gurkan, V. (2022). Sorafenib and Doxorubicin Show Synergistic Effects in Human and Canine Osteosarcoma Cell Lines. Int. J. Mol. Sci., 23.