Abstract
Osteosarcoma (OSA) is an aggressive bone malignancy. Unlike many other malignancies, OSA outcomes have not improved in recent decades. One challenge to the development of better diagnostic and therapeutic methods for OSA has been the lack of well characterized experimental model systems. Spontaneous OSA in dogs provides a good model for the disease seen in people and also remains an important veterinary clinical challenge. We recently used RNA sequencing and qRT-PCR to provide a detailed molecular characterization of OSA relative to non-malignant bone in dogs. We identified differential mRNA expression of the solute carrier family 2 member 1 (SLC2A1/GLUT1), matrix metallopeptidase 3 (MMP3) and nuclear factor erythroid 2–related factor 2 (NFE2L2/NRF2) genes in canine OSA tissue in comparison to paired non-tumor tissue. Our present work characterizes protein expression of GLUT1, MMP3 and NRF2 using immunohistochemistry. As these proteins affect key processes such as Wnt activation, heme biosynthesis, glucose transport, understanding their expression and the enriched pathways and gene ontologies enables us to further understand the potential molecular pathways and mechanisms involved in OSA. This study further supports spontaneous OSA in dogs as a model system to inform the development of new methods to diagnose and treat OSA in both dogs and people.
Highlights
Canine osteosarcoma (OSA) presents a significant veterinary clinical challenge with an estimated incidence rate of between 13.9–27.2/100,000 dogs, considerably higher than the rate in people, 1–3 cases/annum/1,000,000 people [1,2,3,4]
In recent years a detailed understanding of the transcriptional heterogeneity and mechanistic processes in human osteosarcoma has been established by the rigorous unbiased transcriptomic analysis of match tumor and non-malignant specimens [36,37,38,39,40]
Given how common OSA is in dogs and likely genetic contribution to OSA in large breeds, we [16] and others [25, 41,42,43] have sought to extend understanding of the molecular determinants of OSA in dogs and to compare these results to those obtain from OSA from people
Summary
Canine osteosarcoma (OSA) presents a significant veterinary clinical challenge with an estimated incidence rate of between 13.9–27.2/100,000 dogs, considerably higher than the rate in people, 1–3 cases/annum/1,000,000 people [1,2,3,4]. It shares many clinical and molecular features with human OSA [5,6,7,8]. The current management of choice for canine OSA is surgery followed by chemotherapy; the one year survival rarely exceeds 45% even for patients receiving treatment [5, 9,10,11,12,13,14]. Multidrug resistance is a critical limitation to the current success of chemotherapy and, additional therapeutic approaches are needed that could reduce the metastatic rate and recurrence of OSA [17]
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