This application addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DE-101 Molecular Profiling and Developing Mouse Models for Salivary Gland Tumor Research. The proposed work will expand an ongoing successful research program of creating human salivary adenoid cystic carcinoma tumor xenografts in immunodeficient mice to include the other common and clinically aggressive human salivary gland tumor types. The investigators will utilize the resources of the University of Virginia Biorepository, the University of Michigan Tissue Procurement Facility, the NIDCR-sponsored Salivary Gland Tumor Biorepository, the NCI-sponsored Cooperative Human Tissue Network and the Adenoid Cystic Carcinoma Registry to collect viable tumor samples for xenograft implantation. Resulting xenografts will be characterized on the genomic and proteomic level (cytogenetics, array CGH, microarray gene expression profiling, mass spectroscopic analysis of protein phosphorylation). The raw data from these analyses will be made available on a publicly-available website. Special emphasis will be given to creating a stock of viably frozen tissue and creating tissue microarrays of tissue samples from the model, thus creating virtual and real salivary gland tumor resources that investigators may query to create hypotheses of salivary gland tumor biology, and request materials to test those hypotheses. The use of these xenograft model systems include providing raw material for discovery science, a source to derive cell culture lines, reagents for in vivo testing of hypotheses related to salivary gland tumor biology and reagents for preclinical testing of therapeutic strategies for these tumor types.
The study of human salivary gland tumors is hampered by a lack of model systems and tumor tissue to study. We propose to continuously grow salivary gland tumors obtained from patients in mice, which can be used in experiments to understand the molecular basis of these tumors and to test new forms of therapy.
| Chen, Chen; Choudhury, Sujata; Wangsa, Darawalee et al. (2017) A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug. Sci Rep 7:11410 |
| Frierson Jr, Henry F; Moskaluk, Christopher A (2013) Mutation signature of adenoid cystic carcinoma: evidence for transcriptional and epigenetic reprogramming. J Clin Invest 123:2783-5 |
| Moskaluk, Christopher A; Baras, Alexander S; Mancuso, Stefani A et al. (2011) Development and characterization of xenograft model systems for adenoid cystic carcinoma. Lab Invest 91:1480-90 |
