The longterm goal of this research is to examine the molecular events that are responsible for progression of human tumors of the oral cavity and head and neck region. The previous accomplishments of this project have resulted in the characterization of specific tumor cell phenotypes derived from human oral squamous cell carcinomas. these tumor cell subpopulations can be isolated from several tumor types of the oral cavity and will continue to maintain phenotypic characteristics during culture in vitro. Cell populations that exhibit anchorage independence only (AIG), anchorage independence and tumorigenicity (AIGT), and a cell line that can be induced to convert from an AIG to an AIGT phenotype (AIGNT) are among those which have been isolated and will be used in the present proposal. The AIGNT phenotype is of particular interest since MMS treatment can result in a conversion of the cells to the AIGT and AIGT(metastatic) phenotype while benzamide treatment can inhibit the tumorigenic conversion. This plasticity of the AIGNT phenotype provides a tumor cell model system that permits the examination of the molecular changes associated with the onset of tumorigenic potential. Based on the data obtained from our previous research we have formed the hypothesis that, AIGNT cells are capable of a wide range of phenotypic expression.
The specific aims are; 1) To characterize the temporal changes in transformed cell phenotype and protein synthesis following growth in vitro or growth in a surrogate host and compare the cellular phenotypes with the variety present in the original group of cells or tumor. 2) To examine the pattern of expression of tumor suppressor genes in the AIGT and AIGNT phenotypes associated with changes in phenotype and the loss of tumorigenicity. 3) To examine the pattern of expression of cell adhesion molecules in AIGT and AIGNT phenotypes to determine whether changes in the pattern of adhesion to the extracellular matrix occurs and to compare the cell adhesion characteristics of the cell lines with the original tumors and tumors that arise in the surrogate hosts. 4) To examine the basement membrane in AIGT and AIGNT phenotypes to determine the pattern of expression of genes which contribute to both the synthesis and degradation of the basement membrane. These studies will provide molecular data on the biological progression of oral cancer which may be applicable to permitting intervention in the course of human tumors.
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