MOLECULAR-ORAL PATHOLOGY OF NEOPLASTIC PROGRESSION

这项研究的长期目标是检查 与人类口腔和头部肿瘤的进展有关 和颈部。这个项目以前的成就有 结果获得了特定肿瘤细胞表型的特征 来自人类口腔鳞状细胞癌。这些肿瘤细胞亚群 可以从口腔的几种肿瘤类型中分离出来并将 在体外培养过程中继续保持表型特征。 仅表现出锚定独立性(AIG)的细胞群 独立性和致瘤性(AIGT)和一种可诱导的细胞系 从AIG转换为AIGT表型(AIGNT) 已被隔离，并将在本提案中使用。AIGNT 表型特别有趣，因为MMS治疗可以导致 细胞向AIGT和AIGT(转移性)表型的转化 苯甲酰胺治疗可抑制肿瘤转化。这 AIGNT表型的可塑性提供了一种肿瘤细胞模型系统 允许检查与发病相关的分子变化 潜在的致癌能力。基于从我们之前的数据中获得的 研究表明，AIGNT细胞能够 广泛的表型表达。具体目标是：1) 表征转化细胞表型和蛋白质的时间变化 体外生长或在替代宿主中生长后的合成 将细胞表型与原始细胞中存在的变化进行比较 一组细胞或肿瘤。2)研究肿瘤的表达模式 AIGT和AIGNT表型中的抑癌基因与改变相关 在表型和致瘤性丧失方面。3)考察...的模式 细胞黏附分子在AIGT和AIGNT表型中的表达 确定黏附到细胞外的模式是否发生变化 并比较细胞的黏附特性 与原始肿瘤和在代孕体中出现的肿瘤相一致 主持人。4)检测AIGT和AIGNT表型的基底膜 确定基因的表达模式，这些基因对 基底膜的合成和降解。这些研究将 提供口腔癌生物学进展的分子数据 可能适用于允许在人类肿瘤过程中进行干预。

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.