01046-A: The Relevance of Ezrin in the Metastatic Progression of Canine Osteosarcoma

Grant Status: Closed

Grant Amount: $11,925
Sung Hyeok Hong, DVM, PhD; National Cancer Institute
August 1, 2008 - July 31, 2009

Sponsor(s): Akita Club of America, Inc., American Boxer Charitable Foundation, American Bullmastiff Association, American Shih Tzu Club, Inc., Flat-Coated Retriever Foundation, German Wirehaired Pointer Club of America, Golden Retriever Foundation, Great Dane Club of America, Great Dane Club of America Charitable Trust, Great Pyrenees Club of Puget Sound, Greyhound Club of America, Irish Setter Club of America Foundation, Irish Wolfhound Association of the West Coast, Irish Wolfhound Club of America, Inc., Jeffrey Pepper, Leonberger Health Foundation, Mastiff Club of America, Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, Saluki Health Research, Inc., Starlight Fund

Breed(s): -All Dogs
Research Program Area: Oncology - Osteosarcoma
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Project Summary

To-date our work to understand ezrin�s role in cancer spread has been limited to mouse and human OS. In order that pet dogs benefit from the development of novel ezrin related therapies and that clinical trials that include pet dogs can be integrated into the development of new therapies, it is necessary to confirm our ezrin findings in canine OS cells. We have made substantial progress in developing and characterizing canine osteosarcoma cells that we can include in the study of this aggressive and metastatic bone tumor. The study of osteosarcoma biology in canine using these cells can now be aligned with current efforts in our laboratory using murine and human osteosarcoma cells. The collective outcome of this work will be to improve outcomes for canine and pediatric OS patients. We have previously studied the role of ezrin, a cytoskeleton linker protein, in mouse OS cell lines. These studies have led us to believe that the contribution provided by ezrin to the metastatic phenotype may be blocked through the use of PKC inhibitors. Using our newly characterized OS cell lines we have similarly connected ezrin and PKC signaling in canine OS. These data begin to pave the way towards therapeutic studies against osteosarcoma using clinically available PKC inhibitors.

Publication(s)

Hong, S.-H., Osborne, T., Ren, L., Briggs, J., Mazcko, C., Burkett, S. S., & Khanna, C. (2011). Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells. Veterinary and Comparative Oncology, 9(3), 207–218. https://doi.org/10.1111/j.1476-5829.2010.00249.x

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