MOLECULAR-ORAL PATHOLOGY OF NEOPLASTIC PROGRESSION

肿瘤进展的分子口腔病理学

• 批准号: 3167066
• 负责人: GEORGE E MILO
• 金额: $ 25.29万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3167066
• 关键词: SDS polyacrylamide gel electrophoresis; athymic mouse; basement membrane; cell adhesion molecules; cell growth regulation; cell population study; chemical carcinogenesis; clone cells; gene expression; head /neck neoplasm; human tissue; integrins; molecular oncology; neoplasm /cancer transplantation; neoplastic growth; neoplastic transformation; northern blottings; oral pharyngeal neoplasm; phenotype; phenylamide; polymerase chain reaction; protein biosynthesis; protein structure function; squamous cell carcinoma; tissue /cell culture; transfection; tumor antigens; tumor suppressor genes

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.

这项研究的长期目标是检查分子事件， 负责口腔和头部的人类肿瘤的进展 颈部区域。 该项目的前期成果 导致特定肿瘤细胞表型的表征， 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， 在体外培养期间继续保持表型特征。 仅表现出锚定不依赖性（AIG）的细胞群体，锚定 独立性和致瘤性（AIGT）的细胞系，以及可以诱导 从AIG转化为AIGT表型（AIGNT）的人是其中之一， 已被分离，并将用于本提案。 AIGNT 表型是特别令人感兴趣的，因为MMS治疗可以导致 细胞转化为AIGT和AIGT（转移性）表型， 苯甲酰胺治疗可抑制肿瘤发生转化。 这 AIGNT表型的可塑性提供了肿瘤细胞模型系统， 允许检查与发病相关的分子变化 有致瘤的潜力。 根据我们之前的数据， 研究我们已经形成了这样的假设，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 在体外生长或在替代宿主中生长后合成， 将细胞表型与原始细胞中存在的品种进行比较， 细胞或肿瘤。2)检测肿瘤的表达模式 AIGT和AIGNT表型中的抑制基因与 表型和致瘤性的丧失。3)研究…的模式 AIGT和AIGNT表型中细胞粘附分子的表达， 确定粘附到细胞外基质的模式是否发生变化， 基质发生，并比较细胞的细胞粘附特性 与原始肿瘤和在替代物中产生的肿瘤的线 hosts. 4)为了检测AIGT和AIGNT表型的基底膜， 确定基因的表达模式，这有助于两个 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， 可以适用于允许在人类肿瘤过程中进行干预。