This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The strongest single predictor of disease-specific survival at the time of diagnosis in oral and head and neck cancer is the presence or absence of tumor metastasis in the regional lymph nodes. Despite aggressive treatment of regional metastatic disease, cure rates for patients with pathologically positive cervical nodes is 50% lower than cure rates in patients without nodal metastasis. Although metastasis is a major source of mortality in oral and head and neck cancer, little is known about the molecular mechanisms that allow for the distant dissemination of tumor. Characterization of metastasis-associated biomarkers may allow metastasis-prone tumors to be identified prior to distant spread, as well as provide markers that better predict the presence of distant occult disease and/or response to therapy. In addition, a comprehensive understanding of the mechanisms of metastasis may lead to the identification of targets for novel therapeutic interventions. The hypothesis of this project is that metastatic oral and head and neck tumors differ from non-metastatic tumors in the type and abundance of proteins expressed. In addition, it is hypothesized that some alterations will be associated with differences in disease-specific survival, disease-free survival, and response to treatment. The rationale for the hypothesis that metastatic tumors differ from non-metastatic tumors in their protein expression is based (i) the differential expression of genes in metastatic tumors compared to non-metastatic tumors; (ii) the differential expression of proteins in metastatic oral and head and neck cancer cell lines compared to non-metastatic cell lines. This research will expand upon earlier studies of oral and head and neck cancer metastasis by: (1) examining the proteomic complement to the genomic alterations observed in metastatic head and neck cancer; (2) providing insight into the protein alterations that occur within metastatic tumors in vivo as compared to cell lines; (3) determining whether changes in the proteomic profile are associated with clinically relevant parameters.
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